Inhibition of agonist-induced human platelet activation by nitric oxide

G. H R Rao, Leopoldo Raij, B. B. Lester, J. G. White

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations

Abstract

Recent studies have characterized endothelium-derived relaxing factor (EDRF) as nitric oxide which appears to exert its inhibitory effect on human platelets by elevating intracellular levels of cyclic nucleotides (cyclic AMP, cyclic GMP). In this study we have confirmed nitric oxide to be a potent inhibitor of agonist-induced platelet activation. It effectively blocked thrombin-induced calcium mobilization, and also lowered agonist-elevated calcium levels in Fura-2-loaded platelets. Nitric oxide induced significant elevation of cyclic GMP levels, but did not influence cyclic AMP levels. Elevation of cyclic GMP levels did not result in enhanced phosphorylation of the 49 kDa protein. Furthermore, cell-permeant analogues (dibutyryl cyclic GMP and 8-bromo cyclic GMP, 100 μM) were poor inhibitors of agonist-induced platelet aggregation and calcium mobilization. Inhibitors of cyclic GMP phosphodiesterase (M and B 22948, MY 5445) potentiated the inhibitory action of nitric oxide. However, at the concentrations at which they potentiated, they also were potent inhibitors of platelet function. Although adrenaline has not been implicated as a guanylate cyclase inhibitor, it effectively reversed the effect of nitric oxide on platelet function, even in the presence of cyclic GMP phosphodiesterase inhibitors. In addition to nitric oxide, ascorbic acid, 5-hydroxytryptamine and the prostaglandin endoperoxides also increase cyclic GMP levels in platelets but exert no inhibitory effect on platelet function. The results obtained in this study do not support the concept that nitric oxide exerts its inhibitory effect by elevating cyclic GMP levels. It is a potent inhibitor of platelet function, but the mechanism by which it exerts this effect on platelet activation is not clear.

Original languageEnglish
Title of host publicationNitric oxide from L-arginine: a bioregulatory system: proceedings of a Symposium on Biological Importance of Nitric Oxide. ICS897
EditorsS. Moncada, E.A. Higgs, S. Moncada, E.A. Higgs
PublisherElsevier Science Publishers B.V.
Pages355-363
Number of pages9
ISBN (Print)0444811540
StatePublished - Jan 1 1990
Externally publishedYes
EventA Symposium on Biological Importance of Nitric Oxide -
Duration: Sep 14 1989Sep 15 1989

Other

OtherA Symposium on Biological Importance of Nitric Oxide
Period9/14/899/15/89

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rao, G. H. R., Raij, L., Lester, B. B., & White, J. G. (1990). Inhibition of agonist-induced human platelet activation by nitric oxide. In S. Moncada, E. A. Higgs, S. Moncada, & E. A. Higgs (Eds.), Nitric oxide from L-arginine: a bioregulatory system: proceedings of a Symposium on Biological Importance of Nitric Oxide. ICS897 (pp. 355-363). Elsevier Science Publishers B.V..