Activation of Vascular Smooth Muscle K+Channels by Endothelium-Derived Factors

  • Michel Félétou
  • Paul M. Vanhoutte


Endothelial cells synthesize and release vasoactive mediators in response to various neurohumoral substances (e.g., acetylcholine, ATP, bradykinin, thrombin) and physical stimuli (e.g., shear stress exerted by the flowing blood) (Furchgott and Vanhoutte, 1989). Nitric oxide (NO) produced by the L-arginine—NO synthase pathway and prostacyclin produced from arachidonic acid by cyclooxygenase have been identified as potent endothelium-derived vasodilators (Moncada et al., 1976; Moncada and Vane, 1979; Furchgott and Zawadzki, 1980; Palmer et al., 1987, Palmer 1988). However, not all endothelium-dependent relaxations can be fully explained by the release of either NO or prostacyclin. Indeed, another unidentified substance(s) which hyperpolarizes the underlying vascular smooth muscle cells, termed endothelium-derived hyperpolarizing factor (EDHF), may contribute to endothelium-dependent relaxations (Furchgott and Vanhoutte, 1989; Komori and Vanhoutte, 1990; Félétou and Vanhoutte, 1996a; Mombouli and Vanhoutte, 1997).


Nitric Oxide Vascular Smooth Muscle Cell Porcine Coronary Artery Epoxyeicosatrienoic Acid Canine Coronary Artery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adeagbo, A. S. O., and Malik, K. U., 1990, Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries, J. Pharmacol. Exp. Ther. 252:26–34.PubMedGoogle Scholar
  2. Adeagbo, A. S. O., and Malik, K. U., 1991, Contribution of K + channels to arachidonic acid-induced endothelium-dependent vasodilation in rat isolated perfused mesenteric arteries, J. Pharmacol. Exp. Ther. 258:452–458.PubMedGoogle Scholar
  3. Adeagbo, A. S. O., and Triggle, C. R., 1993, Varying extracellular [K +]: A functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed, J. Cardiovasc. Pharmacol 21:423–429.PubMedCrossRefGoogle Scholar
  4. Akatsuka, Y., Egashira, K., Katsuda, Y., Narishige, T., Ueno, H., Shimokawa, H., and Takeshita, A., 1994, ATP-sensitive potassium channels are involved in adenosine A2 receptor mediated coronary vasodilatation, Cardiovasc. Res. 28:906–911.PubMedCrossRefGoogle Scholar
  5. Alonso-Galicia, M., Drummond, H. A., Reddy, K. K., Falck, J. R., and Roman, R. J., 1997, Inhibition of 20-HETE production contributes to the vascular responses to nitric oxide, Hypertension 29:320–325.PubMedCrossRefGoogle Scholar
  6. Archer, S. L., Huang, J. M. C., Hampl, V, Nelson, D. P., Shultz, P. J., and Weir, E. K., 1994, Nitric oxide and cyclic-GMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cyclic-GMP-dependent protein kinase, Proc. Natl. Acad. Sci. U.S.A. 91:7583–7587.PubMedCrossRefGoogle Scholar
  7. Archer, S. L., Huang, J. M. C., Reeve, H. L., Hampl, V., Tolarova S., Michelakis, E., and Weir, E. K., 1996, Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia, Circ. Res. 78:431–442.PubMedCrossRefGoogle Scholar
  8. Banks, M., Wei, C.-M., Kim, C. H., Burnett, J. C., and Miller, V. M., 1996, Mechanism of relaxations to C-type natriuretic peptide in veins, Am. J. Physiol. 271:H1907–H1911.PubMedGoogle Scholar
  9. Barlow, R. S., and White, R. E., 1998, Hydrogen peroxide relaxes porcine coronary arteries by stimulating BKCa channel activity, Am. J. Physiol. 44:H1283–H1289.Google Scholar
  10. Bauersachs, J., Hecker, M., and Busse, R., 1994, Display of the characteristics of endothelium-derived hyperpolarizing factor by a cytochrome P450-derived arachidonic acid metabolite in the coronary microcirculation, Br. J. Pharmacol 113:1548–1553.PubMedCrossRefGoogle Scholar
  11. Beech, D., and Bolton, T. B., 1989, Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein, Br. J. Pharmacol. 98:851–854.PubMedCrossRefGoogle Scholar
  12. Beny, J.-L., 1990, Endothelial and smooth muscle cells hyperpolarized by bradykinin are not dye coupled. Am. J. Physiol. 258:H836–H841.PubMedGoogle Scholar
  13. Beny, J.-L., and Brunet, P. C., 1988 Electrophysiological and mechanical effects of substance P and acetylcholine on rabbit aorta, J. Physiol. (London) 398:277–289.Google Scholar
  14. Beny, J. L., and Chabaud, F., 1996, Kinins and endothelium-dependent hyperpolarization in porcine coronary arteries, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 41–50.Google Scholar
  15. Bény, J. L., and von der Weid, P. Y., 1991, Hydrogen peroxide, an endogenous smooth muscle cell hyperpolarizing factor, Biochem. Biophys. Res. Commun. 176:378–384.PubMedCrossRefGoogle Scholar
  16. Berg, T., and Koteng, O., 1997, Signalling pathway in bradykinin- and nitric oxide-induced hypotension in the normotensive rat; role of K+-channels, Br. J. Pharmacol 121:1113–1120.PubMedCrossRefGoogle Scholar
  17. Bialecki, R. A., and Stinson-Fisher, C., 1995, KCa channel antagonists reduce NO donor-mediated relaxation of vascular and tracheal smooth muscle, Am. J. Physiol. 12:L152–L159.Google Scholar
  18. Bolotina, V. M., Najibi, S., Palacino, J. J., Pagano, P. J., and Cohen, R. A., 1994, Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle cells, Nature 368:850–853.PubMedCrossRefGoogle Scholar
  19. Bolton, T. B., Lang, R. J., and Takewaki, T., 1984, Mechanism of action of noradrenaline and carbachol on smooth muscle of guinea-pig anterior mesenteric artery, J. Physiol. 351:549–572.PubMedGoogle Scholar
  20. Borda, E. S., Sterin-Borda, L., Gimeno, M. F., Lazzari, M. A., and Gimeno, A. C., 1983, The stimulatory effect of prostacyclin (PGI2) on isolated rabbit and rat aorta is probably associated to the generation of a thromboxane A2 (TXA2) “like material,” Arch. Int. Pharmacodyn. Ther. 261:79–89.PubMedGoogle Scholar
  21. Brayden, J. E.,1990, Membrane hyperpolarisation is a mechanism of endothelium-dependent cerebral vasodilation, Am. J. Physiol. 259:H668–H673.PubMedGoogle Scholar
  22. Brayden, J. E., and Murphy, M. E., 1996, Potassium channels activated by endothelium-derived factors in mesenteric and cerebral resistance arteries, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 137–142.Google Scholar
  23. Bredt, D. S., and Snyder, S. H., 1990, Isolation of nitric oxide synthase, a calmodulin-requiring enzyme, Proc. Natl. Acad. Sci. U.S.A. 87:682–685.PubMedCrossRefGoogle Scholar
  24. Brunet, P. C., and Beny, J.-L. 1989. Substance P and bradykinin hyperpolarize pig coronary artery endothelial cells in primary culture, Blood Vessels 26:228–234.PubMedGoogle Scholar
  25. Busse, R., Fichtner, H., Luckhoff, A., and Kohlhardt, M., 1988, Hyperpolarisation and increased free calcium in acetylcholine-stimulated endothelial cells, Am. J. Physiol. 255:H965–H969.PubMedGoogle Scholar
  26. Bychkov, R., Gollasch, M., Steinke, T., Ried, C., Luft, F. C., and Haller, H., 1998, Calcium-activated potassium channels and nitrate-induced vasodilation in human coronary arteries, J. Pharmacol. Exp. Ther. 285:293–298.PubMedGoogle Scholar
  27. Cabell, F., Weiss, D. S., and Price, J. M., 1994, Inhibition of adenosine-induced coronary vasodilation by block of large-conductance Ca2+ -activated K+ channels, Am. J. Physiol. 36:H1455–H1460.Google Scholar
  28. Cai, W. Q., Bodin, P., Loesch, A., Sexton, A., and Burnstock, G., 1993, Endothelium of human umbilical blood vessels—Ultrastructural immunolocalization of neuropeptides, J. Vasc. Res. 30:348–355.PubMedCrossRefGoogle Scholar
  29. Campbell, W. B., Gebremedhin, D., Pratt, P. F., Harder, D. R., 1996, Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factor, Circ. Res. 78:415–423.PubMedCrossRefGoogle Scholar
  30. Carrier, G. O., Fuchs, L. C., Winecoff, A. P., Giulumian, A. D., and White, R. E., 1997, Nitrovasodilators relax mesenteric microvessels by cyclic-GMP-induced stimulation of Ca-activated K channels, Am. J. Physiol. 42:H76–H84.Google Scholar
  31. Caudill, T. K., Resta, T. C., Kanagy, N. L., and Walker, B. R., 1998, Role of endothelial carbon monoxide in attenuated vasoreactivity following chronic hypoxia, Am. J. Physiol. 44:1025–1030.Google Scholar
  32. Chandy, K. G., and Gutman, G. A., 1995, Voltage-gated potassium channel genes, in Ligand- and Voltage Gated Ion Channels (R. A. North, ed.), CRC Press, Boca Raton, pp. 2–71.Google Scholar
  33. Chataigneau T., Félétou M., Duhault J., and Vanhoutte P. M., 1998a, Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarisation in the guinea-pig carotid artery, Br. J. Pharmacol. 123:574–580.PubMedCrossRefGoogle Scholar
  34. Chataigneau T., Félétou, M., Thollon, C.,. Villeneuve, N., Vilaine, J.-P., Duhault, J., and Vanhoutte., P. M., 1998b, Cannabinoid CB1 receptor and endothelium-dependent hyperpolarisation in guinea-pig carotid, rat mesenteric and porcine coronary arteries, Br. J. Pharmacol. 123:968–974.PubMedCrossRefGoogle Scholar
  35. Chaytor, A. Y., Evens, W. H., and Griffith T. M., 1998, Central role of heterocellular gap junction communication in endothelium-dependent relaxations of rabbit arteries. J. Physiol. (London) 508: 561–573.CrossRefGoogle Scholar
  36. Chen, G., and Cheung, D. W., 1997, Effects of K+ channel blockers on Ach-induced hyperpolarization and relaxation in mesenteric arteries, Am. J. Physiol. 41:H2306–H2312.Google Scholar
  37. Chen, G., and Suzuki, H., 1989a, Some electrical properties of the endothelium-dependent hyperpolarisation recorded from rat arterial smooth muscle cells, J. Physiol. 410:91–106.PubMedGoogle Scholar
  38. Chen, G., and Suzuki, H., 1989b, Direct and indirect action of acetylcholine and histamine on intrapulmonary artery and vein smooth muscles of the rat, Jpn. J. Physiol. 39:51–65.PubMedCrossRefGoogle Scholar
  39. Chen, G., and Suzuki, H., 1990, Calcium dependency of the endothelium-dependent hyperpolarisation in smooth muscle cells of the rabbit carotid artery, J. Physiol. 421:521–534.PubMedGoogle Scholar
  40. Chen, G., Suzuki, H., and Weston, A. H., 1988, Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels, Br. J. Pharmacol. 95:1165–1174.PubMedCrossRefGoogle Scholar
  41. Chen, G., Yamamoto, Y., Miwa, K., and Suzuki, H., 1991, Hyperpolarisation of arterial smooth muscle induced by endothelial humoral substances, Am. J. Physiol. 260:H1888–H1892.PubMedGoogle Scholar
  42. Clapp, L. H., Turcato, S., Hall, S., and Baloch, M., 1998, Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost, Eur. J. Pharmacol. 356:215–224.PubMedCrossRefGoogle Scholar
  43. Coceani, F., and Kelsey, L., 1997, Carbon monoxide formation in the ductus arteriosus in the lamb: Implications for the regulation of muscle tone, Br. J. Pharmacol. 120:599–608.PubMedCrossRefGoogle Scholar
  44. Coceani, F., Kelsey, L., and Seidlitz, E., 1996a, Carbon monoxide-induced relaxation of the ductus arteriosus in the lamb: Evidence against the prime role of guanylyl cyclase, Br. J. Pharmacol. 118:1689–1696.PubMedCrossRefGoogle Scholar
  45. Coceani, F., Kelsey, L., Seidlitz, E., and Korzekwa, K., 1996b, Inhibition of the contraction of the ductus arteriosus to oxygen by 1-aminobenzotriazole, a mechanism-based inactivation of cytochrome P-450, Br. J. Pharmacol 117:1586–1592.PubMedCrossRefGoogle Scholar
  46. Cocks, T. M., King, S. J., and Angus, J. A., 1990, Glibenclamide is a competitive inhibitor of the thromboxane A2 receptor in dog coronary artery in vitro, Br. J. Pharmacol. 100:375–378.PubMedCrossRefGoogle Scholar
  47. Cohen, R. A., and Vanhoutte, P. M., 1995, Endothelium-dependent hyperpolarization—beyond nitric oxide and cyclic GMP, Circulation 92:3337–3349.PubMedCrossRefGoogle Scholar
  48. Cohen, R. A., Plane, F., Najibi, S., Huk, I., Malinski, T., and Garland, C. J., 1997, Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarisation of the rabbit carotid artery, Proc. Natl. Acad. Sci. U.S.A. 94:4193–4198.PubMedCrossRefGoogle Scholar
  49. Corriu, C., Félétou, M., Canet, E., and Vanhoutte, P. M. 1996a, Endothelium-derived factors and hyperpolarisations of the isolated carotid artery of the guinea-pig, Br. J. Pharmacol. 119:959–964.PubMedCrossRefGoogle Scholar
  50. Corriu, C., Félétou, M., Canet, E., and Vanhoutte, P. M., 1996b, Inhibitors of the cytochrome P450- monooxygenase and endothelium-dependent hyperpolarisations in the guinea-pig isolated carotid artery, Br. J. Pharmacol. 117:607–610.PubMedCrossRefGoogle Scholar
  51. Cowan, C. L., and Cohen, R,A., 1991, Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and independent responses, Am. J. Physiol. 261:H830–H835.PubMedGoogle Scholar
  52. Darkow, D. J., Lu, L., and White, R. E., 1997, Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cyclic-GMP, Am. J. Physiol. 41:H2765–H2773.Google Scholar
  53. Dart, C., and Standen, N. B., 1993, Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery, J. Physiol. (London) 471:767–786.Google Scholar
  54. Davies, P. F., Oleson, S. P., Clapham, D. E., Morel, E. M, and Schoen, F. J., 1988, Endothelial communication: State of the art lecture, Hypertension 11:563–572.PubMedCrossRefGoogle Scholar
  55. Davis, K., Grinsburg, R., Bristow, M., and Harrison, D. C., 1980, Biphasic action of prostacyclin in the human coronary artery, Clin. Res. 28:165A.Google Scholar
  56. De Mey, J. G., Claeys, M., and Vanhoutte, P. M., 1982, Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery, J. Pharmacol. Exp. Ther. 222:166–173.PubMedGoogle Scholar
  57. Deutsch, D. G., Goligorsky, M. S., Schmid, P. C., Krebsbach, R. J., Schmid, H. H. O., Das, S. K., Dey, S. K., Arreaza, G., Thorup, C., Stefano, G., and Moore, L. C, 1997, Production and physiological actions of anandamide in the vasculature of the rat kidney, J. Clin. Invest. 100:1538–1546.PubMedCrossRefGoogle Scholar
  58. Devane, W. A., Hanus, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., and Mechoulam, R.,1992, Isolation and structure of a brain constituent that binds to the cannabinoid receptor, Science 258:1946–1949.PubMedCrossRefGoogle Scholar
  59. Di Marzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J. C, and Piomelli, D., 1994, Formation and inactivation of endogenous cannabinoid anandamide in central neurons, Nature 372:686–691.PubMedCrossRefGoogle Scholar
  60. Eckman, D. M., Hopkins, N. O., and Keef, K. D., 1995, Effects of inhibitors of cytochrome P450 pathway on relaxation and hyperpolarisation induced with acetylcholine and lemakalim. Circulation 92:I–751.Google Scholar
  61. Eckman, D. M., Hopkins, N. O., McBride, C., and Keef, K. D., 1998, Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: Role of epoxyeicosatrienoic acid, Br. J. Pharmacol. 124:181–189.PubMedCrossRefGoogle Scholar
  62. Edwards, F. R., Hirst, G. D., and Silverberg, G. D., 1988, Inward rectification in rat cerebral arterioles, involvement of potassium ions in autoregulation, J. Physiol. (London) 404:455–466.Google Scholar
  63. Edwards, G., and Weston, A. H., 1995, Potassium channels in the regulation of vascular smooth muscle tone, in: Pharmacologicol Control of Calcium and Potassium Homeostasis: Biological, Therapeutical and Clinical Aspects (T. Godfraind, G. Mancia, M. P. Abbracchio, L. Aguilar-Bryan, and S. Govoni, eds.), Kluwer Academic Press, Dordrecht, The Netherlands, pp. 85–93.CrossRefGoogle Scholar
  64. Edwards, G., Zygmunt, P. M., Högestät, E. D., and Weston, A. H., 1996, Effects of cytochrome P450 inhibitors on potassium currents in mechanical activity in rat portal vein, Br. J. Pharmacol., 119:691–701.PubMedCrossRefGoogle Scholar
  65. Edwards, G., Dora, K. A., Gardener, M. J., Garland, C. J., and Weston, A. H., 1998, K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 396:269–272.PubMedCrossRefGoogle Scholar
  66. Faraci, F. M., and Heistad, D. D., 1998, Regulation of the cerebral circulation: Role of endothelium and potassium channel, Physiol. Rev. 78:54–75.Google Scholar
  67. Félétou, M., and Vanhoutte, P. M., 1985, Endothelium-derived relaxing factor(s) hyperpolarize(s) coronary smooth muscle. Physiologist 48:325.Google Scholar
  68. Félétou, M., and Vanhoutte, P. M., 1988, Endothelium-dependent hyperpolarisation of canine coronary smooth muscle, Br. J. Pharmacol. 93:515–524.PubMedCrossRefGoogle Scholar
  69. Félétou, M., and Vanhoutte, P. M., 1996a, Endothelium-derived hyperpolarizing factor, Clin. Exp. Pharmacol. Physiol. 23:1082–1090.PubMedCrossRefGoogle Scholar
  70. Félétou M., and Vanhoutte, P. M., 1996b, Biossay of endothelium-derived hyperpolarizing factor in canine arteries, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 25–32.Google Scholar
  71. Félétou, M., Hoeffner, U., and Vanhoutte, P. M., 1989, Endothelium-dependent relaxing factors do not affect the smooth muscle of portal-mesenteric vein. Blood Vessels 26:21–32.PubMedGoogle Scholar
  72. Fukao, M., Hattori, Y., Kanno, M., Sakuma, I., and Kitabatake, A., 1997, Evidence against a role of cytochrome P450-derived arachidonic acid metabolites in endothelium-dependent hyperpolarisation by acetylcholine in rat isolated mesenteric artery, Br. J. Pharmacol., 120:439–446.PubMedCrossRefGoogle Scholar
  73. Fukuta, H., Miwa, K., Hozumi, T., Yamamoto, Y., and Suzuki, H., 1996, Reduction by EDHF of the intracellular calcium concentration in vascular smooth muscle, in Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 143–153.Google Scholar
  74. Fulton, D, McGiff, J. C., and Quilley, J., 1992, Contribution of NO and cytochrome P450 to the vasodilator effect of bradykinin in the rat kidney, Br. J. Pharmacol. 107:722–725.PubMedCrossRefGoogle Scholar
  75. Fulton, D., Mahboudi, K., Mcgiff, J. C., and Quilley, J., 1995, Cytochrome P450-dependent effects of bradykinin in the rat heart, Br. J. Pharmacol 114:99–102.PubMedCrossRefGoogle Scholar
  76. Fulton, D, McGiff, J. C., and Quilley, J., 1998, Pharmacological evaluation of an epoxide as the putative hyperpolarizing factor mediating the nitric oxide-independent vasodilator effect of bradykinin in the rat heart, J. Pharmacol. Exp. Ther. 287:497–503.PubMedGoogle Scholar
  77. Furchgott, R. F., and Jonathiandan, D., 1991, Endothelium-dependent and -independent vasodilatation involving cyclic GMP: Relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 28:52–61.PubMedGoogle Scholar
  78. Furchgott, R. F., and Vanhoutte, P. M., 1989, Endothelium-derived relaxing and contracting factors, FASEB J. 3:2007–2018.PubMedGoogle Scholar
  79. Furchgott, R. F., and Zawadzki, J. V., 1980, The obligatory role of the endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376.PubMedCrossRefGoogle Scholar
  80. Ganz, P., Sandbrock, A. W., Landis, S. C., Leopold, J., Gimbrone, M. A., and Alexander, R. W., 1986, Vasoactive intestinal peptide: Vasodilatation and cyclic AMP generation. Am. J. Physiol. 250:H755– H760.PubMedGoogle Scholar
  81. Garcia-Pascual, A., Labadia, A., Jimenez, E., and Costa, G., 1995, Endothelium-dependent relaxation to acetylcholine in bovine oviductal arteries: Mediation by nitric oxide and changes in apamin-sensitive K + conductance, Br. J. Pharmacol. 115:1221–1230.PubMedCrossRefGoogle Scholar
  82. Garland, C. J., and Plane, F., 1996, Relative importance of endothelium-derived hyperpolarizing factor for the relaxation of vascular smooth muscle in different arterial beds, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 173–179.Google Scholar
  83. Gebremedhin, D., Ma, Y. H., Falck, J. R., Roman, R. J., VanRollins, M., and Harder, D. R., 1992, Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am. J. Physiol. 263:H519–H525.PubMedGoogle Scholar
  84. Gebremedhin, D., Harder, D. R., Pratt, P. F., and Campbell, W. B., 1998, Bioassay of an endothelium-derived hyperpolarizing factor from bovine coronary arteries: Role of a cytochrome P450 metabolite, J. Vasc. Res. 35:274–284.PubMedCrossRefGoogle Scholar
  85. Gidday, J. M., Maceren, R. G., Shah, A. R., Meier, J. A., and Zhu, Y., 1996, KATP channels mediate adenosine-induced hyperemia in retina, Invest. Ophthalmol Visual Sci. 37:2624–2633.Google Scholar
  86. Gordon, J. L., and Martin, W., 1983, Endothelium-dependent relaxation of the pig aorta: Relationship to stimulation of 86Rb efflux from endothelial cells, Br. J. Pharmacol. 79:531–541.PubMedCrossRefGoogle Scholar
  87. Graier, W. F., Simecek, S., and Sturek, M., 1995b, Cytochrome P450 mono-oxygenase-regulated signalling of Ca2+ entry in human and bovine endothelial cells, J. Physiol. (London) 482:259–274.Google Scholar
  88. Graier, W. F., Holzmann, S., Hoebel, B. G., Kukovetz, W. R., and Kostner, G. M., 1996, Mechanisms of L-NG-nitroarginine/indomethacin-resistant relaxation in bovine and porcine coronary arteries, Br. J. Pharmacol. 119:1177–1186.PubMedCrossRefGoogle Scholar
  89. Haeusler, G., and Thorens, 1976, The pharmacology of vaso-active antihypertensives, in: Vascular Neuroeffector Mechanisms (J. A. Bevan et al., eds.), Kargel, Basel, Switzerland, pp. 232–241.Google Scholar
  90. Harder, D. R., Campbell, W. B., Gebremedhin, D., and Pratt, P. F., 1996, Biossay of a cytochrome P450-dependent endothelial-derived hyperpolarizing factor from bovine coronary arteries, in: En- dothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 73–81.Google Scholar
  91. Hardy, P., Abran, D., Hou, X., Lahaie, I., Peri, K. G., Asselin, P., Varma, D. R., and Chemtob, S., 1998, A major role for prostacyclin in nitric oxide-induced ocular vasorelaxation in the piglet, Circ. Res. 83:721–729.PubMedCrossRefGoogle Scholar
  92. Hashitani, H., and Suzuki, H., 1997, K+ channels which contribute to the acetylcholine-induced hyperpolarization in smooth muscle of the guinea-pig submucosal arterioles, J. Physiol. (London) 501:319–329.CrossRefGoogle Scholar
  93. Hasunuma, K., Yamaguchi, T., Rodman, D., O’Brien, R., and McMurtry, I., 1991, Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs, Am. J. Physiol. 260:L97–L104.PubMedGoogle Scholar
  94. Hayabuchi, Y., Nakaya, Y., Matsukoa, S., and Kuroda, Y., 1998, Endothelium-derived hyperpolarizing factor activates Ca2+-activated K+ channels in porcine coronary artery smooth muscle cells, J. Cardiovasc. Pharmacol. 32:642–649.PubMedCrossRefGoogle Scholar
  95. Hecker, M., Bara, A. T., Bauersachs, J., and Busse, R., 1994, Characterization of endothelium-derived hyperpolarizing factor as a cytochrome P450-derived arachidonic acid metabolite in mammals, J. Physiol. 481:407–414.PubMedGoogle Scholar
  96. Heinzel, B., John, M., Klatt, P., Böhme, E., and Mayer, B., 1992, Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase, Biochem. J. 281:627–630.PubMedGoogle Scholar
  97. Herlihy, J. T., Bockman, E. L., Berne, R. M., and Rubio, R., 1976, Adenosine relaxation of isolated vascular smooth muscle. Am. J. Physiol. 239:1239–1243.Google Scholar
  98. Hoang, L. M., and Mathers, D. A., 1998, Internally applied endotoxins and the activation of BK channels in cerebral artery smooth muscle via a nitric oxide-like pathway, Br. J. Pharmacol. 123:5–12.PubMedCrossRefGoogle Scholar
  99. Hu. S., and Kim. H. S., 1993, Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid, Eur. J. Pharmacol. 230:215–221.PubMedCrossRefGoogle Scholar
  100. Illiano, S. C., Nagao, T., and Vanhoutte, P. M., 1992, Calmidazolium, a calmodulin inhibitor, inhibits endothelium-dependent relaxations resistant to nitro-L-arginine in the canine coronary artery, Br. J. Pharmacol. 107:387–392.PubMedCrossRefGoogle Scholar
  101. Imai, S., and Takeda, K., 1967, Effects of vasodilators upon the isolated taenia coli of the guinea-pig, J. Pharmacol. Exp. Ther. 156:557–564.PubMedGoogle Scholar
  102. Ito, Y., Suzuki, H., and Kuriyama, K., 1978, Effects of sodium nitroprusside on smooth muscle cells of rabbit pulmonary artery and portal vein, J. Pharmacol. Exp. Ther. 207:1022–1031.PubMedGoogle Scholar
  103. Ito, Y., Kitamura, K., and Kuriyama, K., 1980a, Actions of nitroglycerin on the membrane and mechanical properties of smooth muscle cells of the coronary artery of the pig, Br. J. Pharmacol. 70:197–204.PubMedCrossRefGoogle Scholar
  104. Ito, Y., Kitamura, K., and Kuriyama, K., 1980b, Nitroglycerin and catecholamine actions on smooth muscle cells of the canine coronary artery, J. Physiol. (London) 309:171–183.Google Scholar
  105. Jackson, W. F., Konig, A., Dambacher, T., and Busse, R., 1993, Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels, Am. J. Physiol. 264:H238–H243.PubMedGoogle Scholar
  106. Kauser, K., and Rubanyi, G. M., 1992, Bradykinin-induced nitro-L-arginine-insensitive endothelium-dependent relaxation of porcine coronary artery is not mediated by bioassayable substances, J. Cardiovasc. Pharmacol. 20:S101–S104.PubMedCrossRefGoogle Scholar
  107. Kauser, K., Stekiel, W. J, Rubanyi, G. M, and Harder, D. R., 1989, Mechanism of action of EDRF on pressurized arteries:Effect on K+ conductance, Circ. Res. 65:199–204.PubMedCrossRefGoogle Scholar
  108. Kawasaki, J., Kobayashi, S., Miyagi, Y., Nishimura, J., Fujishima, M., and Kanaide, H., 1997, The mechanisms of the relaxation induced by vasoactive intestinal peptide in the porcine coronary artery, Br. J. Pharmacol. 121:977–985.PubMedCrossRefGoogle Scholar
  109. Kessler, P., Lischke, V., and Hecker, M., 1996, Etomidate and thiopental inhibit the release of endothelium- derived-hyperpolarizing factor in the human renal artery. Anesthesiology 84:1485–1488.PubMedCrossRefGoogle Scholar
  110. Khan, S. A., Mathews, S. R., and Meisheri, K. D., 1993, Role of calcium-activated K+ channels in vasodilatation induced by nitroglycerin, acetylcholine and nitric oxide, J. Pharmacol Exp. Ther. 267:1327–1335.PubMedGoogle Scholar
  111. Kitazono, T., Ibayashi, S., Nagao, T., Fujii, K., and Fujishima, M., 1997, Role of Ca2+-activated K+ channels in acetylcholine-induced dilatation of the basilar artery in vivo, Br. J. Pharmacol. 120:102–106.PubMedCrossRefGoogle Scholar
  112. Kleppisch T., and Nelson, M. T., 1995, Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptor and c-AMP-dependent protein kinase, Proc. Natl. Acad. Sci. U.S.A. 92:12441– 12445.PubMedCrossRefGoogle Scholar
  113. Knot, H. J., Zimmermann, P. A., and Nelson M. T.,1996, Extracellular potassium-induced hyperpolarization and dilatations of rat coronary and cerebral arteries involve inward rectifier potassium channels, J. Physiol. (London) 492:419–430.Google Scholar
  114. Komori, K., and Suzuki, H., 1987, Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery, Circ. Res. 61:586–593.PubMedCrossRefGoogle Scholar
  115. Komori, K., and Vanhoutte P. M., 1990, Endothelium-derived hyperpolarizing factor, Blood Vessels 27:238–245.PubMedGoogle Scholar
  116. Komori, K., Lorenz, R. R., and Vanhoutte, P. M., 1988, Nitric oxide, ACh and electrical and mechanical properties of canine arterial smooth muscle, Am. J. Physiol. 255:H207–H212.PubMedGoogle Scholar
  117. Krippeit-Drews, P., Haberland, C., Fingerle, J., Drews, G., and Lang, F., 1995, Effects of H2O2 on membrane potential and [Ca2+]i- of cultured rat arterial smooth muscle cells, Biochem. Biophys. Res. Commun. 209:139–145.PubMedCrossRefGoogle Scholar
  118. Kühberger, E., Groschner, K., Kukovetz, W. R., and Brunner, F., 1994, The role of myoendothelial cell contact in non-nitric oxide-, non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery, Br. J. Pharmacol. 113:1289–1294.PubMedCrossRefGoogle Scholar
  119. Kuo, L., and Chancellor, J. D., 1995, Adenosine potentiates flow-induced dilation of coronary arterioles by activating KATP channels in endothelium, Am. J. Physiol. 38:H541–H549.Google Scholar
  120. Li, P. L., and Campbell, W. B., 1998, Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein, Circ. Res. 80:877–884.CrossRefGoogle Scholar
  121. Li, P. L., Zou, A. P., and Campbell, W. B., 1997, Regulation of potassium channels in coronary arterial smooth muscle by endothelium-derived vasodilators, Hypertension 29:262–267.PubMedCrossRefGoogle Scholar
  122. Li, P. L., Jin, M. W., and Campbell, W. B., 1998, Effect of selective inhibition of soluble guanylate cyclase on the KCa channel activity in coronary smooth muscle, Hypertension 31:303–308.PubMedCrossRefGoogle Scholar
  123. Luu, T. N., Dashwood, M. R., Tadjkarimi, S., Chester, A. H., and Yacoub, M. H., 1997, ATP-sensitive potassium channels mediate vasodilatation by calcitonin gene related peptide in human internal mammary but not gastroepiploic arteries, Eur. J. Clin. Invest. 27:960–966.PubMedCrossRefGoogle Scholar
  124. Makujina, S. R., Olanrewaju, H. A., and Mustafa, S. J., 1994, Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels, Am. J. Physiol. 267:H716–H724.PubMedGoogle Scholar
  125. Marchenko, S. M., and Sage, S. O., 1994, Smooth muscle cells affect endothelial membrane potential in rat aorta. Am. J. Physiol. 267:H804–H811.PubMedGoogle Scholar
  126. McCarron, J. G., and Halpern, W., 1990, Potassium dilates rat cerebral arteries by two independent mechanisms, Am. J. Physiol. 259:H902–H908.PubMedGoogle Scholar
  127. Milner, P., Kirkpatrick, K. A., Ralevic, V., Toothill, V., and Burnstock, G., 1990, Endothelial cells cultured from human umbilical vein release ATP and acetylcholine in response to increased flow, Proc. R. Soc. London B. 241:245–248.CrossRefGoogle Scholar
  128. Mistry, D. K., and Garland, C. J., 1998, Nitric oxide (NO)-induced activation of large conductance Ca2+-dependent K+ channels (BKCa) in smooth muscle cells isolated from the rat mesenteric artery, Br. J. Pharmacol. 124:1131–1140.PubMedCrossRefGoogle Scholar
  129. Miura, H., and Gutterman, D. D., 1998, Human coronary arteriolar dilation to arachidonic acid depends on cytochrome P450 monooxygenase and Ca2+-activated K+ channels, Circ. Res. 83:501–507.PubMedCrossRefGoogle Scholar
  130. Miyoshi, H., and Nakaya, Y., 1994, Endotoxin-induced non endothelial nitric oxide activates the Ca2+- activated K+ channel in cultured vascular smooth muscle cells, J. Mol. Cell. Cardiol. 26:1487–1495.PubMedCrossRefGoogle Scholar
  131. Miyoshi, H., and Nakaya, Y., 1995, Calcitonin gene related peptide activates the K+ channels of vascular smooth muscle cells via adenylate cyclase, Basic Res. Cardiol. 90:332–336.PubMedCrossRefGoogle Scholar
  132. Miyoshi, H., Nakaya, Y., and Moritoki, H., 1994, Nonendothelial-derived nitric oxide activates the ATP-sensitive K channel of vascular smooth muscle cells, FEBS Lett. 345:47–49.PubMedCrossRefGoogle Scholar
  133. Mombouli, J.-V., and Vanhoutte, P. M., 1997, Endothelium-derived hyperpolarizing factor(s): Updating the unknown, Trends Pharmacol. Sci. 18:252–256.PubMedCrossRefGoogle Scholar
  134. Mombouli, J. V., Illiano, S., Nagao, T., and Vanhoutte, P. M., 1992, The potentiation of bradykinin-induced relaxations by perindoprilat in canine coronary arteries involves both nitric oxide and endothelium- derived hyperpolarizing factor, Circ. Res. 71:137–144.PubMedCrossRefGoogle Scholar
  135. Mombouli, J.-V., Bissiriou, I., and Vanhoutte, P. M., 1996, Biossay of endothelium-derived hyperpolarizing factor: Is endothelium-derived depolarizing factor a confounding element?, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 51–57.Google Scholar
  136. Moncada, S., and Vane, J. R., 1979, Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin, Pharmacol. Rev. 30:293–331.Google Scholar
  137. Moncada, S., Gryglewski, R. J., Bunting, S., and Vane, J. R., 1976, An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation, Nature 263:663–665.PubMedCrossRefGoogle Scholar
  138. Moncada, S., Herman, A. G., Higgs, E. A., and Vane, J. R., 1977, Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the antithrombotic properties of vascular endothelium, Thromb. Res. 11:323–344.PubMedCrossRefGoogle Scholar
  139. Moncada, S., Palmer, R. J. M., and Higgs, E. A., 1991, Nitric oxide: Physiology, pathophysiology, and pharmacology, Pharmacol Rev. 43:109–142.PubMedGoogle Scholar
  140. Mügge, A., Lopez, J. A. G., Piegors, D. J., Breese, K. R., and Heistad, D. D., 1991, Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine, Am. J. Physiol. 260:H242–H247.PubMedGoogle Scholar
  141. Murphy, M. E., and Brayden, J. E., 1995a, Apamin-sensitive K+ channels mediate an endothelium-dependent hyperpolarization in rabbit mesenteric arteries, J. Physiol. 489:723–734.PubMedGoogle Scholar
  142. Murphy, M. E., and Brayden, J. E., 1995b, Nitric oxide hyperpolarisation of rabbit mesenteric arteries via ATP-sensitive potassium channels, J. Physiol. 486:47–58.PubMedGoogle Scholar
  143. Mutafova-Yambolieva, V. N., and Keef, K. D., 1997, Adenosine-induced hyperpolarization in guinea-pig coronary artery involves A2B receptors and KATP channels, Am. J. Physiol. 42:H2687–H2695.Google Scholar
  144. Nagao, T., and Vanhoutte, P. M., 1992a, Characterization of endothelium-dependent relaxations resistant to nitro-L-arginine in the porcine coronary artery, Br. J. Pharmacol. 107:1102–1107.PubMedCrossRefGoogle Scholar
  145. Nagao, T., and Vanhoutte, P. M., 1992b, Hyperpolarisation as a mechanism for endothelium-dependent relaxations in the porcine coronary artery, J. Physiol. 445:355–367.PubMedGoogle Scholar
  146. Nagao, T., Illiano, S. C., and Vanhoutte, P. M., 1992a, Heterogeneous distribution of endothelium-dependent relaxations resistant to NG-nitro-L-arginine in rats, Am. J. Physiol. 263:H1090–H1094.PubMedGoogle Scholar
  147. Nagao, T., Illiano, S. C., and Vanhoutte, P. M., 1992b, Calmodulin antagonists inhibit endothelium-dependent hyperpolarisation in the canine coronary artery, Br. J. Pharmacol. 107:382–386.PubMedCrossRefGoogle Scholar
  148. Najibi, S., and Cohen, R. A., 1995, Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO, Am. J. Physiol. 38:H805–H811.Google Scholar
  149. Nakashima, M., and Vanhoutte, P. M., 1995, Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium channels in vascular smooth muscle of the canine saphenous vein, J. Pharmacol. Exp. Ther. 272:379–384.PubMedGoogle Scholar
  150. Nakashima, M., Mombouli, J.-V., Taylor, A. A., and Vanhoutte, P. M., 1993, Endothelium-dependent hyperpolarisation caused by bradykinin in human coronary arteries, J. Clin. Invest. 92:2867–2871.PubMedCrossRefGoogle Scholar
  151. Nazario, B., Hu, R. M., Pedram, A., Prins, B., and Levin, E. R., 1995, Atrial and brain natriuretic peptides stimulate the production and secretion of C-type natriuretic peptide from bovine aortic endothelial cells, J. Clin. Invest. 95:1151–1157.PubMedCrossRefGoogle Scholar
  152. Needleman, P., Jakshik, B., and Johnson, E. M., 1973, Sulfhydryl requirement for relaxation of vascular smooth muscle, J. Pharmacol. Exp. Ther. 187:324–331.PubMedGoogle Scholar
  153. Nees, S., Gerbes, A. L., Willershausen-Zonnchen, B., and Gerlach, E., 1980, Purine metabolism in cultured coronary endothelial cells, Adv. Exp. Med. Biol. 122:25–30.CrossRefGoogle Scholar
  154. Nelson, M. T., and Quayle, J. M., 1995, Physiological roles and properties of potassium channels in arterial smooth muscle, Am. J. Physiol. 268:C799–C822.PubMedGoogle Scholar
  155. Nelson, M. T., Huang, Y., Brayden, J. E., Hescheler, J., and Standen, N. B., 1990, Arterial dilations in response to calcitonin gene related peptide involve activation of K+ channels, Nature, 344:770–773.PubMedCrossRefGoogle Scholar
  156. Nishiyama, M., Hashitani, H., Fukuta, H., Yamamoto, Y., and Suzuki, H., 1998, Potassium channels activated in the endothelium-dependent hyperpolarization in guinea-pig coronary artery, J. Physiol. (London) 510:455–465.CrossRefGoogle Scholar
  157. Node, K., Kitazake, M., Kosaka, H., Minamino, T., Sato, H., Kuzuya, T., and Hori, M., 1997, Roles of NO and Ca2+-activated K+ channels in coronary vasodilatation induced by 17-beta-estradiol in ischemic heart failure, FASEB J. 11:793–799.PubMedGoogle Scholar
  158. Nossaman, B. D., Kaye, A. D., Feng, C. J., and Kadowitz, P. J., 1997, Effects of charybdotoxin on responses to nitrovasodilators and hypoxia in the rat lung, Am. J. Physiol. 16:L787–L791.Google Scholar
  159. Ohlmann, P., Martinez, M. C., Schneider, F., Stoclet, J. C., and Andriantsitohaina, R., 1997, Characterization of endothelium-derived relaxaing factors released by bradykinin in human resistance arteries, Br. J. Pharmacol. 121:657–664.PubMedCrossRefGoogle Scholar
  160. Olanrewaju, H. A., Hargittai, P. T., Lieberman, E. A., and Mustafa, S. J., 1995, Role of endothelium in hyperpolarisation of coronary smooth muscle by adenosine and its analogues, J. Cardiovasc. Pharmacol. 25:234–239.PubMedCrossRefGoogle Scholar
  161. Olanrewaju, H. A, Hargittai, P. T, Lieberman, E. M., and Mustafa, S. J., 1997, Effect of ouabain on adenosine receptor-mediated hyperpolarization in porcine coronary artery smooth muscle, Eur. J. Pharmacol. 322:185–190.PubMedCrossRefGoogle Scholar
  162. Oltman, C. L., Weintraub, N. L., VanRollins, M., and Dellsperger, K. C., 1998, Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation, Circ. Res. 83:932–939.PubMedCrossRefGoogle Scholar
  163. Onoue, H., and Katuzic, Z. S., 1997, Role of potassium channels in relaxations of canine middle cerebral arteries induced by nitric oxide donors, Stroke 28:1264–1270.PubMedCrossRefGoogle Scholar
  164. Ozaka, T., Doi, Y., Kayashima, K., and Fujimoto, S., 1997, Weibel-Palade bodies as a storage site of calcitonin gene related peptide and endothelin-1 in blood vessels of the rat carotid body, Anat. Rec. 247:388–394.PubMedCrossRefGoogle Scholar
  165. Pacicca, C., von der Weid, P., and Beny, J. L. 1992. Effect of nitro-L-arginine on endothelium-dependent hyperpolarisations and relaxations of pig coronary arteries, J. Physiol. 457:247–256.PubMedGoogle Scholar
  166. Palmer, R. M. J., Ferridge, A. G., and Moncada, S., 1987, Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor, Nature 327:524–526.PubMedCrossRefGoogle Scholar
  167. Palmer, R. M. J., Ashton, D. S., and Moncada, S., 1988, Vascular endothelial cells synthesize nitric oxide from L-arginine, Nature 333:664–666.PubMedCrossRefGoogle Scholar
  168. Parkington, H. C., Tare, M., Tonta, M. A., and Coleman, H. A., 1993, Stretch revealed three components in the hyperpolarisation of guinea-pig coronary artery in response to acetylcholine, J. Physiol 465:459–476.PubMedGoogle Scholar
  169. Parkington, H. C., Tonta, M., Coleman, H., and Tare, M., 1995, Role of membrane potential in endothelium-dependent relaxation of guinea-pig coronary arterial smooth muscle, J. Physiol. 484:469–480.PubMedGoogle Scholar
  170. Parkington, H. C, Tare, M., and Hammarstrm, A. K. M., 1996, The role of endothelium-derived prostacyclin in regulating tone in vascular smooth muscle, in: Endothelium-Derived Hyperpolarizing Factor (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 57–64.Google Scholar
  171. Pascoal, I. F., and Umans, J. G., 1996, Effect of pregnancy on mechanisms of relaxation in human omental microvessels, Hypertension 28:183–187.PubMedCrossRefGoogle Scholar
  172. Pataricza, J., Toth, G. K., Penke, B., Hohn, J., and Papp, J. G., 1995, Effect of selective inhibition of potassium channels on vasorelaxing response to cromakalim, nitroglycerin and nitric oxide of canine coronary arteries, J. Pharm. Pharmacol. 47:921–925.PubMedCrossRefGoogle Scholar
  173. Peng, W., Hoidal, J. R., and Farrukh, I. S., 1996, Regulation of Ca2+-activated K+ channels in pulmonary vascular smooth muscle cells — role of nitric oxide, J. Appl. Physiol. 81:1264–1272.PubMedGoogle Scholar
  174. Petersson, J., Zygmunt, P. M., Brandt, L., and Högestatt, E. D., 1995, Substance P-induced relaxation and hyperpolarisation in human cerebral arteries, Br. J. Pharmacol. 115:889–894.PubMedCrossRefGoogle Scholar
  175. Petersson, J., Zygmunt, P. M., and Högestätt, E. D., 1997, Characterization of the potassium channels involved in EDHF-mediated relaxation in cerebral arteries, Br. J. Pharmacol. 120:1344–1350.PubMedCrossRefGoogle Scholar
  176. Pfister, S. L., Spitzbarth, N., Nithipatikom, K., Edgemond, W. S., and Campbell W. B., 1999, Endothelium-derived eicosanoids from lipoxygenase relax the rabbit aorta by opening potassium channels, in: Endothelium-Dependent Hyperpolarizations Vol. 2 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, 1999, pp. 17–28.Google Scholar
  177. Plane, F., and Garland, C. J., 1994, Smooth muscle hyperpolarization and relaxation to acetylcholine in the rabbit basilar artery, J. Autonom. Nerv. Syst. 49:S15–S18.CrossRefGoogle Scholar
  178. Plane, F., Pearson, T., and Garland, C. J., 1995, Multiple pathways underlying endothelium-dependent relaxation in the rabbit in isolated femoral artery, Br. J. Pharmacol. 115:31–38.PubMedCrossRefGoogle Scholar
  179. Plane, F. Hurrell, A. Jeremy, J. Y., and Garland, C. J., 1996, Evidence that potassium channels make a major contribution to SIN-1-evoked relaxation of rat isolated mesenteric artery, Br. J. Pharmacol. 119:1557– 1562.PubMedCrossRefGoogle Scholar
  180. Plane, F., Holland, M., Waldron, G. J., Garland, C. J., and Boyle, J. P., 1997, Evidence that anandamide and EDHF act via different mechanisms in the rat isolated mesenteric arteries, Br. J. Pharmacol. 121: 1509–1511.PubMedCrossRefGoogle Scholar
  181. Plane, F., Wiley, K. E., Jeremy, J. Y., Cohen, R. A., and Garland, C. J., 1998, Evidence that different mechanisms underlie smooth muscle relaxation to nitric oxide and nitric oxide donors in the rabbit isolated carotid artery. Br. J. Pharmacol. 123:1351–1358.PubMedCrossRefGoogle Scholar
  182. Pomerantz, K., Sinterose, A., and Ramwell, P., 1978, The effect of prostacyclin on the human umbilical artery, Prostaglandins 15:1035–1044.PubMedCrossRefGoogle Scholar
  183. Popp, R., Bauersachs, J., Sauer, E., Hecker, M., Fleming, I., and Busse, R., 1996, A transferable, β- naphthoflavone-inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells, J. Physiol (London) 497:699–709.Google Scholar
  184. Prasad, K., and Bharadwaj, L. A., 1996, Hydroxyl radical — a mediator of acetylcholine induced vascular relaxation, J. Mol. Cell. Cardiol. 28:2033–2041.PubMedCrossRefGoogle Scholar
  185. Pratt, P. F., Edgemont, W. S., Hillard, C. J., and Campbell, W. B., 1998, N-Arachidonylethanolamide relaxation of bovine coronary arteries is not mediated by CB1 cannabinoid receptor, Am. J. Physiol. 274:H375–H381.PubMedGoogle Scholar
  186. Price, J. M., and Hellermann, A., 1997, Inhibition of cyclic-GMP mediated relaxation in small rat coronary arteries by block of Ca++-activated K+ channels, Life Sci. 61:1185–1192.PubMedCrossRefGoogle Scholar
  187. Prior, H. M., Webster, N., Quinn, K., Beech, D. J., and Yates, M. S.,1998, K+-induced dilation of a small renal artery: No role for inward rectifier K+ channels, Cardiovasc. Res. 37:780–790.PubMedCrossRefGoogle Scholar
  188. Quignard, J.-F., Chataigneau, T., Corriu, C., Duhault, J., Félétou, M., and Vanhoutte, P. M, 1999a, Effects of SIN-1 on potassium channels of vascular smooth muscle cells of the rabbit aorta and guinea-pig carotid artery, in: Endothelium-Dependent Hyperpolarizations Factor (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 193–200.Google Scholar
  189. Quignard, J.-F., Félétou, M., Thollon, C., Vilaine, J. P., Duhault, J., and Vanhoutte, P. M, 1999b, Potassium ions and endothelium-derived hyperpolarizing factors in guinea-pig carotid and porcine coronary arteries. Br. J. Pharmacol. 127:27–34.PubMedCrossRefGoogle Scholar
  190. Quignard, J.-F., Chataigneau, T., Corriu, C., Duhault, J., Félétou, M., and Vanhoutte, P. M, 1999c, Potassium channels involved in EDHF-induced hyperpolarization of the smooth muscle cells of the isolated guinea-pig carotid artery, in: Endothelium-Derived Hyperpolarization Factor (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 201–208.Google Scholar
  191. Quilley, J., Fulton, D., and McGiff, J. C., 1997, Hyperpolarizing factors, Biochem. Pharmacol. 54:1059–1070.PubMedCrossRefGoogle Scholar
  192. Randall, M. D., and Kendall, D. A., 1997, Involvement of a cannabinoid in endothelium-derived hyper-Qpolarizing factor-mediated coronary vasorelaxation, Eur. J. Pharmacol. 335:205–209.PubMedCrossRefGoogle Scholar
  193. Randall, M. D., and Kendall, D. A., 1998, Anandamide and endothelium-derived hyperpolarizing factor act via a common vasorelaxant mechanism in rat mesentery. Eur. J. Pharmacol. 346:51–53.PubMedCrossRefGoogle Scholar
  194. Randall, M. D., Alexander, S. P. H., Bennett, T., Boyd, E. A., Fry, J. R., Gardiner, S. M., Kemp, P. A., Mcculloch, A. I., and Kendall, D. A., 1996, An endogenous cannabinoid as an endothelium-derived vasorelaxant, Biochem. Biophys. Res. Commun. 229:114–120.PubMedCrossRefGoogle Scholar
  195. Randall, M. D., Mcculloch, A. I., and Kendall, D. A., 1997, Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery, Eur. J. Pharmacol. 333:191–197.PubMedCrossRefGoogle Scholar
  196. Rapacon, M., Mieyal, P., McGiff, J. C., Fulton, D., and Quilley, J., 1996, Contribution of calcium-activated potassium channels to the vasodilator effect of bradykinin in the isolated, perfused kidney of the rat, Br. J. Pharmacol. 118:1504–1508.PubMedCrossRefGoogle Scholar
  197. Rees, D. D., Palmer, R. M. J., Hodson, H. F., and Moncada, S., 1989, A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation, Br. J. Pharmacol. 96:418–424.PubMedCrossRefGoogle Scholar
  198. Richard, V., Tanner, F. C., Tschudi, M. R., and Lüscher, T. F., 1990, Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. Am. J. Physiol 259:H1433–H1439.PubMedGoogle Scholar
  199. Robertson, B. E., Schubert, R., Hescheler, J., and Nelson, M. T., 1993, cyclic-GMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am. J. Physiol. 265:C299–C303.PubMedGoogle Scholar
  200. Rosenblum, W. I., 1987, Hyodoxyl radical mediates the endothelium-dependent relaxation produced by bradykinin in mouse cerebral arterioles, Circ. Res. 61:601–603.PubMedCrossRefGoogle Scholar
  201. Rosolowski, M., and Campbell, W. B., 1993, Role of PGI2 and EETs in the relaxation of bovine coronary arteries to arachidonic acid, Am. J. Physiol. 264:H327–H335.Google Scholar
  202. Rosolowski, M., and Campbell, W. B., 1996, Synthesis of hydroxyeicosatetraenoic (HETEs) and epoxy-eicosatrienoic acids (EETs) by cultured bovine coronary endothelial cells, Biochim. Biophys. Acta 1299:267–277.CrossRefGoogle Scholar
  203. Rubanyi, G.,M., and Vanhoutte, P. M., 1986, Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle, Am. J. Physiol 250:H815–H821.PubMedGoogle Scholar
  204. Rubanyi, G. M., and Vanhoutte, P. M., 1987, Nature of endothelium-derived relaxing factor: Are there two relaxing mediators?, Circ. Res. 61:II61–II67.PubMedGoogle Scholar
  205. Ruiz, E., and Tejerina, T., 1998, Relaxant effects of L-citrulline in rabbit vascular smooth muscle, Br. J. Pharmacol. 125:186–192.PubMedCrossRefGoogle Scholar
  206. Schubert, R., Serebryakov, N. V., Engel, H., and Hopp, H. H., 1996, Iloprost activates KCa channels of vascular smooth muscle cells: Role of cyclic-AMP-dependent proteine kinase, Am. J. Physiol. 271:C1203–C1211.PubMedGoogle Scholar
  207. Schubert, R., Serebryakov, N. V., Mewes, H., and Hopp, H. H., 1997, Iloprost dilates rat small arteries: Role of KATP and KCa channel activation by cyclic-AMP-dependent protein kinase, Am. J. Physiol. 272:H1147–H1156.PubMedGoogle Scholar
  208. Sedaa, K. O., Bjur, R. A., Shinozuka, K., and Westfall, D. P., 1990, Nerve and drugs-induced release of adenine nucleosides and nucleotides from rabbit aorta, J. Pharmacol. Exp. Ther. 252:1060–1067.PubMedGoogle Scholar
  209. Sheridan, B. C., Mclntyre, R. C., Meldrum, D. R., and Fullerton, D. A., 1997, KATP channels contribute to beta and adenosine receptor-mediated pulmonary vasorelaxation, Am. J. Physiol. 17:L950–L956.Google Scholar
  210. Shimizu, S., and Paul, R. J., 1998, The endothelium-dependent, substance P relaxation of porcine coronary arteries resistant to nitric oxide synthesis inhibition is partially mediated by 4-aminopyridine-sensitive voltage-dependent K+ channels. Endothelium 5:287–295.CrossRefGoogle Scholar
  211. Shimokawa, H., Flavahan, N. A., Lorenz, R. R., and Vanhoutte, P. M., 1988, Prostacyclin releases endothelium-derived relaxing factor and potentiates its action in coronary arteries of the pig, Br. J. Pharmacol. 95:1197–1203.PubMedCrossRefGoogle Scholar
  212. Shin, J. H., Chung, S., Park, E. J., Uhm, D. Y., and Suh, C. K., 1997, Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer, FEBS Lett. 415:299–302.PubMedCrossRefGoogle Scholar
  213. Shinozuka, K., Hashimoto, M., Bjur, R. A., Westfall, W. P., and Hattori, K., 1994, In vitro studies of release of adenine nucleotides and adenosine from rat vascular endothelium in response to α1-adrenoceptor stimulation, Br. J. Pharmacol. 113:1203–1208.PubMedCrossRefGoogle Scholar
  214. Shryock, J. C., Rubio, R., and Berne, R. M., 1988, Release of adenosine from pig aortic endothelial cells during hypoxia and metabolic inhibition, Am. J. Physiol. 254:H223–H229.PubMedGoogle Scholar
  215. Siegel, G., Stock, G., Schnalke, F., and Litza, B., 1987, Electrical and mechanical effects of prostacyclin in canine carotid artery, in: Prostacyclin and Its Stable Analogue Iloprost (R. J. Gryglewski and G. Stock, eds.), Springer-Verlag, Berlin, pp. 143–149.CrossRefGoogle Scholar
  216. Siegel, G., Mironneau, J., Schnalke, F., Schroder, G., Schulz, B. G., and Grote, J., 1990, Vasodilatation evoked by K+ channel opening, Prog. Clin. Biol. Res. 327:229–306.Google Scholar
  217. Siegel, G., Emden, J., Wenzel, K., Mironneau, J., and Stock G., 1992, Potassium channel activation and vascular smooth muscle, Adv. Exp. Med. Biol. 311:53–72.PubMedCrossRefGoogle Scholar
  218. Simonsen, U., Garcia-Sacristan A., and Prieto, D., 1997, Apamin-sensitive K+ channels involved in the inhibition of acetylcholine-induced contractions in lamb coronary small arteries, Eur. J. Pharmacol. 329:153–163.PubMedGoogle Scholar
  219. Smits, P., Williams, S. B., Lipson, D. E., Banitt, P., Ronge, G. A., and Creager, M. A., 1995, Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans, Circulation 92:2135–2141.PubMedCrossRefGoogle Scholar
  220. Standen, N. B., Quayle, J. M., Davies, N. W., Brayden, J. E., Huang, Y., and Nelson, M. T., 1989, Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle, Science 245:177–180.PubMedCrossRefGoogle Scholar
  221. Sundquist, T., 1991, Bovine aortic endothelial cells release hydrogen peroxide, J. Cell. Physiol. 148:152–156.CrossRefGoogle Scholar
  222. Suzuki, H., Chen, G., Yamamoto, Y., and Miwa, K., 1992, Nitroarginine-sensitive and insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery, Jpn. J. Physiol. 42:335–347.PubMedCrossRefGoogle Scholar
  223. Taguchi, H., Heistad, D. D., Chu, Y., Rios, C. D., Ooboshi, H., and Faraci, F. M., 1996, Vascular expression of inducible nitric oxide synthase isoform associated with activation of Ca++-dependent K+ channels, J. Pharmacol. Exp. Ther. 279:1514–1519.PubMedGoogle Scholar
  224. Taniguchi, J., Furukawa, K. I., and Shigekawa, M., 1993, Maxi K+ channels are stimulated by cyclic guanosine monophosphate-dependent protein kinase in canine coronary artery smooth muscle cells, Pflügers Arch. Eur. J. Physiol. 423:167–172.CrossRefGoogle Scholar
  225. Tare, M., Parkington, H. C., Coleman, H. A., Neild, T. O., and Dusting, G. J., 1990, Hyperpolarisation and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium, Nature 346:69–71.PubMedCrossRefGoogle Scholar
  226. Taylor, H. J., Chaytor, A. T., Evans, W. H., and Griffith, T. M., 1998, Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18β-glycyrrhetinic acid, Br. J. Pharmacol. 125:1–3.PubMedCrossRefGoogle Scholar
  227. Taylor, S. G., Southerton, J. S., Weston, A. H., and Baker, J. R. J., 1988, Endothelium-dependent effects of acetylcholine in rat aorta: A comparison with sodium nitroprusside and cromakalim, Br. J. Pharmacol. 94:853–863.PubMedCrossRefGoogle Scholar
  228. Urakami-Harasawa, L., Shimokawa, H., Nakashima, M., Egashira, K., and Takeshita, A., 1997, Importance of endothelium-derived hyperpolarizing factor in human arteries, J. Clin. Invest. 100:2793–2799.PubMedCrossRefGoogle Scholar
  229. Van de Voorde, J., Vanheel, B., and Leusen, I., 1992, Endothelium-dependent relaxation and hyperpolarisation in aorta from control and renal hypertensive rats, Circ. Res. 70:1–8.PubMedCrossRefGoogle Scholar
  230. Vanhoutte, P. M., 1998, An old-timer makes a come-back, Nature 396:213–216.PubMedCrossRefGoogle Scholar
  231. Vanhoutte, P. M., and Félétou, M., 1996, Conclusion: Existence of multiple EDHF(s)?, in: Endothelium- Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte ed.), Harwood Academic Publishers, Amsterdam, pp. 303–307.Google Scholar
  232. von der Weid, P.-Y., 1998, ATP-sensitive K+ channels in smooth muscle cells of guinea-pig lymphatics: Role in nitric oxide and β-adrenoceptor agonist-induced hyperpolarizations, Br. J. Pharmacol. 125:17–22.PubMedCrossRefGoogle Scholar
  233. Wallerstedt, S. M., and Bodelsson, M., 1997, Endothelium-dependent relaxations by substance P in human isolated omental arteries and veins: Relative contribution of prostanoids, nitric oxide and hyperpolarisation,Br. J. Pharmacol. 120:25–30.PubMedCrossRefGoogle Scholar
  234. Wang, R., 1998, Resurgence of carbon monoxide: An endogenous gaseous vasorelaxing factor, Can. J. Physiol. Pharmacol. 76:1–15.PubMedCrossRefGoogle Scholar
  235. Wang, R., and Wu, L. Y., 1997, The chemical modification of KCa channels by carbon monoxide in vascular smooth muscle cells, J. Biol Chem. 272:8222–8226.PubMedCrossRefGoogle Scholar
  236. Wang, R., Wang, Z. Z., and Wu, L. Y., 1997a, Carbon-monoxide-induced vasorelaxation and the underlying mechanisms. Br. J. Pharmacol. 121:927–934.PubMedCrossRefGoogle Scholar
  237. Wang, R., Wu, L. Y., and Wang, Z. Z., 1997b, The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells, Pflügers Arch. Eur. J. Physiol. 434:285–291.CrossRefGoogle Scholar
  238. Wei, C. M., Hu, S., Miller, V. M., and Burnett, J. C., 1994, Vascular actions of C-type natriuretic peptide in isolated porcine coronary arteries and coronary vascular smooth muscle cells, Biochem. Biophys. Res. Commun. 205:765–771.PubMedCrossRefGoogle Scholar
  239. Weidelt, T., Boldt, W., and Markwardt, F. 1997, Acetylcholine-induced K+ currents in smooth muscle of intact rat small arteries, J. Physiol. (London) 500:617–630.Google Scholar
  240. Weintraub, N. L., Stephenson, A. L., Sprague, R. S., and Lonigro, A. J., 1999, Role of phospholipase A2 in EDHF-mediated relaxation of the porcine coronary artery, in: Endothelium-Dependent Hyperpolarizations,Vol. 2 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 97–108.Google Scholar
  241. Wellman, G. C., Bonev, A. D., Nelson, M. T., and Brayden, J. E., 1996, Gender differences in coronary artery diameter involve estrogen, nitric oxide and Ca2+-dependent K+ channels, Circ. Res. 79:1024–1030.PubMedCrossRefGoogle Scholar
  242. Wellman, G. C., Quayle, J. M., and Standen, N. B., 1998, ATP-sensitive K+ channel activation by calcitonin gene related peptide and protein kinase A in pig coronary arterial smooth muscle, J. Physiol (London) 507:117–129.CrossRefGoogle Scholar
  243. White, R., and Hiley, C. R., 1997, A comparison of EDHF-mediated responses and anandamide-induced relaxations in the rat isolated mesenteric artery, Br. J. Pharmacol. 122:1573–1584.PubMedCrossRefGoogle Scholar
  244. White, R., and Hiley, C. R., 1998, The actions of some cannabinoid receptor ligands in the rat isolated mesenteric artery, Br. J. Pharmacol. 125:533–541.PubMedCrossRefGoogle Scholar
  245. Wise, H., and Jones, R. L., 1996, Focus on prostacyclin and its novel mimetics, Trends Pharmacol. Sci. 17:17–21.PubMedCrossRefGoogle Scholar
  246. Yamamoto, Y., Fukuta, H., Nakahira, Y., and Suzuki, H., 1998, Blockade by 18β-glycyrrhetinic acid of intercellular electrical coupling in guinea-pig arterioles. J. Physiol (London) 511:501–508.CrossRefGoogle Scholar
  247. Yamanaka, A., Ishikawa, K., and Goto, K., 1998, Characterization of endothelium-dependent relaxation independent of NO and prostaglandins in guinea-pig coronary artery, J. Pharmacol. Exp. Ther. 285:480–489.PubMedGoogle Scholar
  248. Zanzinger, J., Czachurski, J., and Seller, H., 1996, Role of calcium-dependent K+ channels in the regulation of arterial and venous tone by nitric oxide in pigs, Pflügers Arch. Eur. J. Physiol. 432:671–677.CrossRefGoogle Scholar
  249. Zhang, H., Stockbridge, N., Weir, B., Krueger, C., and Cook, D., 1991, Glibenclamide relaxes vascular smooth muscle constriction produced by prostaglandin F, Eur. J. Pharmacol 195:27–35.PubMedCrossRefGoogle Scholar
  250. Zhao, Y. J., and Wang, J., 1996, Pulmonary vasoconstriction effects of prostacyclin in rats: Potential role of thromboxane receptors, J. Appl. Physiol. 81:2595–2603.PubMedGoogle Scholar
  251. Zhao, Y. J., Wang, J., Rubin, L. J., and Yuan, X. J., 1997, Inhibition of Kv and KCa channels antagonizes NO-induced relaxation in pulmonary artery, Am. J. Physiol. 41:H904–H912.Google Scholar
  252. Zou, A. P., Fleming, J. T., Falck, J. R., Jacobs, E. R., Gebremedhin, D., Harder, D. R., and Roman, R. J., 1996, 20-Hydroxyeicosatetraenoic acid is an endogenous inhibitor of the large conductance Ca++- activated K+ channel in renal arterioles, Am. J. Physiol. 270:R228–R237.PubMedGoogle Scholar
  253. Zygmunt, P. M., and Högestätt, E. D., 1996, Endothelium-dependent hyperpolarization and relaxation in the hepatic artery of the rat, in: Endothelium-Derived Hyperpolarizing Factor, Vol. 1 (P. M. Vanhoutte, ed.), Harwood Academic Publishers, Amsterdam, pp. 191–202.Google Scholar
  254. Zygmunt, P. M., Grundsmar, L., and Högestätt, E. D., 1994a. Endothelium-dependent relaxation resistant to Nω-nitro-L-arginins in the rat hepatic artery and aorta, Acta Physiol. Scand. 152:107–114.PubMedCrossRefGoogle Scholar
  255. Zygmunt, P. M., Högestätt, E. D., and Grundemar, L., 1994b, Light-dependent effects of zinc protoporphyrin IX on endothelium-dependent relaxation resistant to Nω-nitro-L-arginine, Acta Physiol. Scand. 152:137– 143.PubMedCrossRefGoogle Scholar
  256. Zygmunt, P. M., Edwards, G., Weston; A. H., Davis, S. C., and Högestätt, E. D., 1996, Effects of cytochrome P450 inhibitors on EDHF-mediated relaxation in the rat hepatic artery, Br. J. Pharmacol 118:1147– 1152.PubMedCrossRefGoogle Scholar
  257. Zygmunt, P. M., Edwards, G., Weston, A. H., Larsson, B., and Högestätt, E. D., 1997a, Involvement of voltage-dependent potassium channels in the EDHF-mediated relaxation of rat hepatic artery. Br. J. Pharmacol 121:141–149.PubMedCrossRefGoogle Scholar
  258. Zygmunt, P. M., Högestätt, E. D., Waldeck, K., Edwards, G., Kirkup A. J., and Weston, A. H., 1997b, Studies on the effects of anmdamide in rat hepatic artery, Br. J. Pharmacol. 122:1679–1686.PubMedCrossRefGoogle Scholar
  259. Zygmunt, P. M., Plane F., Paulsson, M., Garland, C. J., and Högestätt, E. D., 1998, Interactions between endothelium-derived relaxing factors in the rat hepatic artery: Focus on regulation of EDHF, Br. J. Pharmacol 124:992–1000.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Michel Félétou
    • 1
  • Paul M. Vanhoutte
    • 2
  1. 1.Département de DiabétologieInstitut de Recherches ServierSuresnesFrance
  2. 2.Institut de Recherches Internationales ServierCourbevoieFrance

Personalised recommendations