Relaxation of Vascular Smooth Muscle by Organic Nitrates: Ideas and Hypotheses on a Still Unsolved Problem
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.
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- 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
- Diamond, J. and Blisard, K. S., Mol. Pharmacol. 12: 688–692 (1975).Google Scholar
- Horowitz, P. M., Adams, J. B., Wood, K. S. and Ignarro, L. J., Abstract. Fed. Proc. 44: 1816 (1985).Google Scholar
- Doyle, M. P., Pickering, R. A., da Conceiçao, J. J., Biol. Chem. 259: 80–87 (1984).Google Scholar
- Bennett, B. M., Brien, J. F., Nakatsu, K. and Marks, G. S. J., Pharmacol. Exp. Ther. 234: 228–232 (1985).Google Scholar
- 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
- Bennett, B. M., Brien, J. F., Nakatsu, K., McLaughlin, B. E., Kobus, S. and Marks, G. S. (unpublished observations).Google Scholar
- 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
- 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
- Popescu, L. M., Panoiu, C., Hinescu, M. and Nutu, O. Eur. J., Pharmacol. 107: 393–394 (1985).Google Scholar