Advertisement

Relaxation of Vascular Smooth Muscle by Organic Nitrates: Ideas and Hypotheses on a Still Unsolved Problem

  • G. S. Marks
  • B. M. Bennett
  • J. F. Brien
  • K. Nakatsu
  • B. E. McLaughlin

Summary

Several hypotheses on the mechanism of relaxation of vascular smooth muscle by organic nitrates have been considered. On the basis of the evidence available it was concluded that the vasorelaxant effects of organic nitrates are not mediated by prostaglandins. Nor did the evidence available support the notion of a “key sulfhydryl” group in an “organic nitrate receptor.” The biotransformation of GTN to GDN has been shown to occur concurrently with relaxation. It appears that nitric oxide, released from organic nitrates or organic nitrites, interacts with a heme moiety associated with guanylate cyclase, resulting in activation of the enzyme. The idea that S-nitrosothiols are the proximate moieties which activate guanylate cyclase is controversial. The evidence suggests that increased levels of cGMP, resulting from guanylate cyclase activation, enhances the activity of a cGMP-dependent protein kinase and that this is followed by dephosphorylation of myosin light chain and relaxation of vascular smooth muscle.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Chamberlain, D. A., Int. J. Cardiol. 7: 157 (1985).CrossRefGoogle Scholar
  2. [2]
    Levin, R. I., Jaffe, E. A., Weksler, B. B. and Tack-Goldman, K. J., Clin. Invest. 67: 762–769 (1981).CrossRefGoogle Scholar
  3. [3]
    Schrör, K., Grodzinska, L. and Darius, H., Thromb. Res. 23: 59–67 (1981).PubMedCrossRefGoogle Scholar
  4. [4]
    Bennett, B. M., Moffat, J. A., Armstrong, P. W. and Marks, G. S., Can. J. Physiol. Pharmacol. 61: 554–560 (1983).PubMedCrossRefGoogle Scholar
  5. [5]
    Bennett, B. M. and Marks, G. S., Trends in Pharmacol. Sci. 5: 329–332 (1984).CrossRefGoogle Scholar
  6. [6]
    Furchgott, R. F., Ann. Rev. Pharmacol. Toxicol. 24: 175–197 (1984).CrossRefGoogle Scholar
  7. [7]
    Martin, W. M., Villani, G. M., Jothianadan, D. and Furchgott, R. F., J. Pharmacol. Exp. Ther. 232: 708–716 (1985).PubMedGoogle Scholar
  8. [8]
    Needleman, P. and Johnson, E. M. Jr., J. Pharmacol. Exp. Ther. 184: 709–715 (1973).PubMedGoogle Scholar
  9. [9]
    Moffat, J. A., Armstrong, P. W. and Marks, G. S., Can. J. Physiol. Pharmacol. 60: 1261–1266 (1982).PubMedCrossRefGoogle Scholar
  10. [10]
    Ignarro, L. J., Lippton, H., Edwards, J. C., Baricos, W. H., Hyman, A. L., Kadowitz, P. J. and Gruetter, C. A., J. Pharmacol. Exp. Ther. 218: 739–749 (1981).PubMedGoogle Scholar
  11. [11]
    Armstrong, J. A., Marks, G. S. and Armstrong, P. W., Mol. Pharmacol. 18: 112–116 (1980).PubMedGoogle Scholar
  12. [12]
    Brien, J. F., McLaughlin, B. E., Breedon, T. H., Bennett, B. M., Nakatsu, K. and Marks, G. S., Abstract. Proc. Can. Fed. Biol. Soc. 28: 172 (1985).Google Scholar
  13. [13]
    Ignarro, L. J. and Kadowitz, P., J. Ann. Rev. Pharmacol. Toxicol. 25: 171–191 (1985).CrossRefGoogle Scholar
  14. [14]
    Craven, P.A. and DeRubertis, F. R., Biochim. Biophys. Acta, 745: 310–321 (1983).PubMedCrossRefGoogle Scholar
  15. [15]
    Diamond, J. and Blisard, K. S., Mol. Pharmacol. 12: 688–692 (1975).Google Scholar
  16. [16]
    Kobayashi, A., Suzuki, Y., Kamikawa, T., Hayashi, H. and Yamazaki, N., Life Sci. 27: 1679–1685 (1980).PubMedCrossRefGoogle Scholar
  17. [17]
    Waldman, S.A., Sinacore, MS., Lewicki, J. A., Chang, L. Y. and Murad, F., J. Biol. Chem. 259: 4038–4042 (1984).PubMedGoogle Scholar
  18. [18]
    Gerzer, R., Hofmann, F., and Schultz, G., Eur. J„Biochem. 116: 479–486 (1981).PubMedCrossRefGoogle Scholar
  19. [19]
    Gerzer, R., Böhme, E., Hofmann, F. and Schultz, G., FEBS Lett. 132: 71–74 (1981).PubMedCrossRefGoogle Scholar
  20. [20]
    Horowitz, P. M., Adams, J. B., Wood, K. S. and Ignarro, L. J., Abstract. Fed. Proc. 44: 1816 (1985).Google Scholar
  21. [21]
    Doyle, M. P., Pickering, R. A., da Conceiçao, J. J., Biol. Chem. 259: 80–87 (1984).Google Scholar
  22. [22]
    Bennett, B. M., Nakatsu, K., Brien, J. F. and Marks, G. S., Can. J. Physiol. Pharmacol. 62: 704–706 (1984).PubMedCrossRefGoogle Scholar
  23. [23]
    Bennett, B. M., Brien, J. F., Nakatsu, K. and Marks, G. S. J., Pharmacol. Exp. Ther. 234: 228–232 (1985).Google Scholar
  24. [24]
    Bennett, B. M., Brien, J. F., Nakatsu, K., Kobus, S. and Marks, G. S., Abstract. Proc. Can. Fed. Biol. Soc. 28: 57 (1985).Google Scholar
  25. [25]
    Needleman, P. and Hunter, Jr., F. E., Mol. Pharmacol. 1: 77–86 (1965).PubMedGoogle Scholar
  26. [26]
    Needleman, P. and Harkey, A. B., Biochem. Pharmacol. 20: 1867–1876 (1971).PubMedCrossRefGoogle Scholar
  27. [27]
    Bennett, B. M., Brien, J. F., Nakatsu, K., McLaughlin, B. E., Kobus, S. and Marks, G. S. (unpublished observations).Google Scholar
  28. [28]
    Zelis, R. and Flaim, S. F., Ann. Int. Med. 94: 124 (1981).PubMedGoogle Scholar
  29. [29]
    Kreye, V. A. W. and Schlicker, E., in Vascular Neuroeffector Mechanisms (Bevan, J. A., ed) pp 4–6, Raven Press, New York (1980).Google Scholar
  30. [30]
    Ginsburg, R., Bristow, M. R., Gordon, J., van Breemen, C., Stinson, E. B. and Harrison, D. C., Abstract, Circulation 64, Suppl. IV, IV–122 (1981).Google Scholar
  31. [31]
    Rapoport, R. M., Draznin, M. B. and Murad, F., Nature (Lond.) 306: 174–176 (1983).CrossRefGoogle Scholar
  32. [32]
    Rapoport, R. M., Draznin, M. B. and Murad, F., Trans. Assoc. Am. Physicians 96: 19–30 (1983).PubMedGoogle Scholar
  33. [33]
    Rapoport, R. M., Draznin, M. B. and Murad, F., Circ. Res. 55: 468–479 (1984).PubMedGoogle Scholar
  34. [34]
    Johnson, R. M. and Lincoln, T. M., Mol. Pharmacol. 27: 333–342 (1985).PubMedGoogle Scholar
  35. [35]
    Popescu, L. M., Panoiu, C., Hinescu, M. and Nutu, O. Eur. J., Pharmacol. 107: 393–394 (1985).Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH, Braunschweig 1986

Authors and Affiliations

  • G. S. Marks
  • B. M. Bennett
  • J. F. Brien
  • K. Nakatsu
  • B. E. McLaughlin

There are no affiliations available

Personalised recommendations