Skip to main content
SpringerLink
Log in

Endothelium-Dependent Vasodilation and the Nature of the Endothelium-Derived Relaxing Factor

  • Chapter
Book cover Vascular Endothelium

Abstract

In 1980, Furchgott and Zawadzki reported that the relaxation of the smooth muscle of in vitro preparations of rabbit aorta and other arteries induced by acetylcholine and other agonists for muscarinic receptors was dependent on the presence of endothelial cells in the preparations. After complete removal of the endothelial cells, either mechanically or enzymatically, acetylcholine no longer induced any relaxation, but in most arteries, actually caused some contraction at higher concentrations (Figure 1). In the case of isolated rings or strips of rabbit thoracic aorta, the muscarinic receptor mediating relaxation appeared to be the same subtype (M2) as the receptor on the smooth muscle cells mediating contraction (Furchgott et al., 1981; Furchgott, 1986).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Angus, J.A., Campbell, G.R., Cocks, T.M., and Henderson, J.A. Vasodilation by acetylcholine is endothelium-dependent. A study by sonomicrometry in canine femoral artery in vivo. J. Physiol. 344:209–222, 1983.

    PubMed  CAS  Google Scholar 

  • Cherry, P.D., Furchgott, R.F., Zawadzki, J.V., and Jothianandan, D. The role of endothelial cells in the relaxation of isolated arteries by bradykinin. Proc. Natl. Acad. Sci. USA. 79:2105–2110, 1982.

    Article  Google Scholar 

  • Cocks, T.H., Angus, J.A., Campbell, J.H., and Campbell, G.R. Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. J. Cell Physiol. 123:310–320, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Diamond, J. and Chu, E.D. Possible role for cyclic GMP in endothelium-dependent relaxation of rabbit aorta by acetylcholine. Comparison with nitroglycerin. Res. Comm. Chem. Pathol. Pharmacol. 41:369–381, 1983.

    CAS  Google Scholar 

  • Feletou, M. and Vanhoutte, P.M. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br. J. Pharmacol. 93:515–524, 1988.

    Article  PubMed  CAS  Google Scholar 

  • Forstermann, U. and Neufang, B. Endothelium-dependent vasodilation by melittin: are lipoxygenase products involved? Am. J. Physiol. 249:1114–1119, 1985.

    Google Scholar 

  • Forstermann, U., Trogisch, C. and Busse, R. Species-dependent differences in the value of endothelium-derived vascular relaxing factor. Eur. J. Pharmacol. 106:639–643, 1985.

    Article  Google Scholar 

  • Forstermann, U., Mulsch, A., Bohme, E. and Busse, R. Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries. Circ. Res. 58:531–538, 1986a.

    Article  PubMed  CAS  Google Scholar 

  • Forstermann, U., Gopple-Strube, M., Frolich, J.C. and Busse, R. Inhibitors of acyl-coenzyme A lysolecithin acyltransferase activate the production of endothelium-derived vascular relaxing factor. J. Pharmacol Exp. Ther. 238:352–359, 1986b.

    PubMed  CAS  Google Scholar 

  • Furchgott, R.F. Role of endothelium in responses of vascular smooth muscle. Circ. Res. 53:557–573, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Furchgott, R.F. Role of endothelium in the responses of vascular smooth muscle to drugs. Ann. Rev. Pharmacol. Toxicol. 24:175–197, 1984.

    Article  CAS  Google Scholar 

  • Furchgott, R.F. Will pharmacological procedures for receptor classification continue to be useful in the future? Recent research supporting an affirmative answer. In Perspectives on Receptor Classification, ed. by J. Black, P. Gerskowitch and D. Jenkinson, pp. 269–280 Alan R. Liss, New York, 1986.

    Google Scholar 

  • Furchgott, R.F. Endothelium-dependent relaxation in systemic arteries. In Relaxing and Contracting Factors, ed. by P.M. Vanhoutte, Humana Press, Clifton, p.p. 1–26, 1988.

    Chapter  Google Scholar 

  • Furchgott, R.F. Studies on relaxation of rabbit aorta by sodium nitrite: the basis for the proposal that the acid-activatable inhibitory factor from retractor penis is inorganic nitrite and the endothelium-derived relaxing factor is nitric oxide. In Mechanisms of Vasodilatation, ed. by P.M. Vanhoutte, Raven Press, New York. p.p. 401–414, 1988b.

    Google Scholar 

  • Furchgott, R.F., Zawadzki, J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376, 1980.

    Article  PubMed  CAS  Google Scholar 

  • Furchgott, R.F., Zawadzki, J.V. and Cherry, P.D. Role of endothelium in the vasodilator response to acetylcholine. In Vasodilatation, ed. by P.M. Vanhoutte and T. Leusen, Raven Press, New York, pp. 49–66, 1981.

    Google Scholar 

  • Furchgott, R.F., Cherry, P.D. and Zawadzki, J.V. Endothelial cells as mediators of vasodilation of arteries. J. Cardiovasc. Pharmacol. 6:Suppl. 3, S336–S344, 1984.

    Article  PubMed  Google Scholar 

  • Furchgott, R.F., Martin, W., Cherry, P.D., Jothianandan, D. and Villani, G.M. Endothelium-dependent relaxation, photorelaxation and cyclic GMP. In Vascular Neuroeffector Mechanisms, ed. by T. Bevan, R. Godfraind, R. Maxwell, J.C. Stoclet and M. Worcel, Elsevier, Amsterdam, pp. 105–114, 1985.

    Google Scholar 

  • Furchgott, R.F., Carvalho, M.H., Khan, M.T. and Matsunaga, K. Evidence for endothelium-dependent vasodilation of resistance vessels by acetylcholine. Blood Vessels 24:145–149, 1987.

    PubMed  CAS  Google Scholar 

  • Furchgott, R.F., Khan, M.T., Jothianandan, D. and Khan, A.S. Evidence that endothelium-derived factor of rabbit aorta is nitric oxide. In Vascular Neuroeffector Mechanisms, ed. by J.A. Bevan, H. Majewski, R.A. Maxwell and D.F. Story, IRL Press, Oxford, pp. 77–84 1988.

    Google Scholar 

  • Griffith, T.M., Edwards, D.H., Lewis, M.J., Newby, A.C. and Henderson, A.H. The nature of the endothelium-derived vascular relaxant factor. Nature 308:645–647, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Griffith, T.M., Edwards, D.H., Newby, A.C., Lewis, M.J., and Henderson, A.H. Production of endothelium-derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium. Cardiovasc. Res. 20:7–12, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Griffith, T.M., Edwards, D.H., Davies, R.L.T., Harrison, T.J. and Evans, K.T. EDRF coordinates the behavior of vascular resistance vessels. Nature 329:442–445, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Gruetter, C.A., Barry, B.K., McNamara, D.B., Gruetter, D.Y., Kadowitz, P.J. and Ignarro, L.J. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J. Cyclic Nucleotide Res. 5:211–224, 1979.

    PubMed  CAS  Google Scholar 

  • Gruetter, C.A., Gruetter, D.Y., Lyon, J.E., Kadowitz, P.J. and Ignarro, L.J. Relationship between cyclic guanosine 3′:5′-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: effects of methylene blue and methemoglobin. J. Pharmacol. Exp. Ther. 219:181–186, 1981.

    PubMed  CAS  Google Scholar 

  • Gryglewski, P.J., Palmer, R.M., and Moncada, S.A. Superoxide anion is involved in the breakdown of endothelium-derived relaxing factor. Nature 320:454–456, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Holzmann, S. Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips. J. Cyclic Nucleotide Res. 8:409–419, 1982.

    PubMed  CAS  Google Scholar 

  • Ignarro, L.J., Harbison, R.G., Wood, K.S. and Kadowitz, P.J. Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: Stimulation by acetylcholine, bradykinin and arachidonic acid. J. Pharmacol. Exp. Ther. 237:893–900, 1986.

    PubMed  CAS  Google Scholar 

  • Ignarro, L.J., Buga, G.M., Wood, K.S., Byrns, R.E. and Chaudhuri, G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad Sci. USA 84:9265–9269, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Ignarro, L.J., Byrns, R.E. and Wood, K.S. Biochemical and pharmacological properties of endothelium-derived relaxant factor and its similarity to nitric oxide radical. In Mechanisms of Vasodilation, ed. by P.M. Vanhoutte, Raven Press, New York, pp. 427–435, 1988.

    Google Scholar 

  • Khan, M.T. and Furchgott, R.F. Kinetics of inactivation of endothelium-derived relaxing factor released from endothelial cells of rabbit aorta. Blood Vessels 23:81–82, 1986. abstr.

    Google Scholar 

  • Khan, M.R. and Furchgott, R.F. Additional evidence that endothelium-derived relaxing factor is nitric oxide. In Pharmacology, ed. by M.J. Rand and C. Raper, Elsevier, Amsterdam, pp. 341–344 1987.

    Google Scholar 

  • Komori, K. and Suzuki, H. Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery. Circ. Res. 61:586–593, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Long, C.J. and Stone, T.W. The release of endothelium-derived relaxant factor is calcium dependent. Blood Vessels 22:205–208, 1985.

    PubMed  CAS  Google Scholar 

  • Long, C.J., Shikano, K. and Berkowitz, B.A. Anion exchange resin discriminates between nitric oxide and EDRF. Eur. J. Pharm. 142:317, 1987.

    Article  CAS  Google Scholar 

  • Martin, W., Villani, G.M., Jothianandan, D. and Furchgott, R.F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J. Pharmacol Exp. Ther. 232:708–716, 1985a.

    PubMed  CAS  Google Scholar 

  • Martin, W., Villani, G.M., Jothianandan, D. and Furchgott, R.F. Blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation of rabbit aorta by certain ferrous hemoproteins. J. Pharmacol. Exp. Ther. 233:679–685, 1985b.

    PubMed  CAS  Google Scholar 

  • Martin, W., Furchgott, R.F., Villani, G.M. and Jothianandan, D. Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor (EDRF). J. Pharmacol. Exp. Ther. 237:529–538, 1986a.

    PubMed  CAS  Google Scholar 

  • Martin, W., Furchgott, R.F., Villani, G.M. and Jothianadan, D. Phosphodiesterase inhibitors induce endothelium-dependent relaxation of rat and rabbit aorta by potentiating the effects of spontaneously released endothelium-derived relaxing factor (EDRF). J. Pharmacol. Exp. Ther. 237:539–547, 1986b.

    PubMed  CAS  Google Scholar 

  • Moncada, S., Palmer, R.M.J. and Gryglewski, R.J. Mechanism of action of some inhibitors of endothelium-derived relaxing factor. Proc. Natl. Acad. Sci. USA 83:9164–9168, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Murad, F., Arnold, W.P., Mittal, C.K. and Braughier, J.M. Properties and regulation of guanylate cyclase and some proposed functions of cyclic GMP. Adv. Cyclic Nucleotide Res. 11:175–204, 1979.

    PubMed  CAS  Google Scholar 

  • Palmer, R.M.J., Ferrige, A.G. and Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Pohl, U., Dezsi, L., Simon, B. and Busse, R. Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo. Am. J. Physiol. 253:H234–H239, 1987.

    PubMed  CAS  Google Scholar 

  • Rapoport, R.M. and Murad, F. Agonist-induced endothelium-dependent relaxations in rat thoracic aorta may be mediated through cGMP. Circ. Res. 52:352–357, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Rubanyi, G.M. and Vanhoutte, P.M. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am. J. Physiol. 250:H822–H827, 1986.

    PubMed  CAS  Google Scholar 

  • Rubanyi, G.M., Lorenz, R.R. and Vanhoutte, P.M. Bioassay of endothelium-derived relaxing factor(s): Inactivation by catecholamines. Am. J. Physiol. 215:H1077–H1080, 1985.

    Google Scholar 

  • Secrest, R.J., Olsen, E.J., and Chapnick, B.M. Leukotriene D4 relaxes canine renal and superior mesenteric arteries. Circ. Res. 57:323–329, 1985.

    Article  PubMed  Google Scholar 

  • Shikano, K., Ohlstein, E.H., and Berkowitz, B.A. Differential selectivity of endothelium-derived relaxing factor and nitric oxide in smooth muscle. Br. J. Pharmacol. 92:483–485, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Singer, H.A. and Peach, M.J. Calcium and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. Hypertension 4, Suppl. 3, 11–19 – 11–25, 1982.

    Article  Google Scholar 

  • Stewart, D.J., Munzel, T. and Bassenge, E. Reversal of acetylcholine-induced coronary resistance vessel dilation by hemoglobin. Eur. J. Pharmacol. 136:339–342, 1987.

    Article  Google Scholar 

  • Thorn, S., Hughes, A., and Sever, P.S. Endothelium-dependent responses in human arteries. In Relaxing and Contracting Factors, ed. by P.M. Vanhoutte, Humana Press, Clifton, N.J., pp. 511–528 1988.

    Google Scholar 

  • Vanhoutte, P.M., Rubanyi, G.M., Miller, V.M. and Houston, D.S. Modulation of vascular smooth muscle contraction by the endothelium. Ann. Rev. Physiol. 48:307–320, 1986.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Health Science Center, State University of New York, Brooklyn, New York, USA

    Robert F. Furchgott

Authors
  1. Robert F. Furchgott
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Georgia, Augusta, Georgia, USA

    John D. Catravas

  2. Yale University School of Medicine, New Haven, Connecticut, USA

    C. Norman Gillis

  3. University of Miami School of Medicine, Miami, Florida, USA

    Una S. Ryan

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Press, New York

About this chapter

Cite this chapter

Furchgott, R.F. (1989). Endothelium-Dependent Vasodilation and the Nature of the Endothelium-Derived Relaxing Factor. In: Catravas, J.D., Gillis, C.N., Ryan, U.S. (eds) Vascular Endothelium. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-8532-5_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-8532-5_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-8534-9

  • Online ISBN: 978-1-4684-8532-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation