Inhibition of human platelet aggregation by endothelium-derived relaxing factor, sodium nitroprusside or lloprost is potentiated by captopril and reduced thiols

V. Mollace, D. Salvemini, W. C. Sessa, J. R. Vane

Research output: Contribution to journalArticle

Abstract

We have examined whether inhibitors of angiotensin-converting enzyme-containing sulfhydryl groups such as, captopril (CPT) or SQ 14,534, the nonsulfhydryl-containing angiotensin-converting enzyme inhibitors, teprotide (TPR) or enalaprilat (ENA) and other structurally unrelated sulfhydryl-containing compounds, N-2-mercaptopropionylglycine (MPG) or N-acetyl-L-cysteine (NAC), could influence platelet aggregation. Incubation of human washed platelets with CPT, SQ 14,534, TPR, ENA, MPG or NAC (0.1-0.5 mM) did not modify their aggregatory responses to thrombin. However, the antiaggregatory properties of endothelial cells cultured from bovine aorta were potentiated by CPT, SQ 14,534, MPG or NAC but not by TPR or ENA (40-100 μM). CPT (100-500 μM) or NAC (50-200 μM) but not ENA (100 and 500 μM) also potentiated the antiaggregatory effects of sodium nitroprusside (1.0 μM) or iloprost (0.2 nM). The ability of the thiol-containing compounds (CPT or NAC) to potentiate the antiaggregatory effects of sodium nitroprusside or iloprost was not associated with an elevation of platelet cyclic GMP or cyclic AMP levels, respectively. Thus, CPT and other sulfhydryl-containing compounds can synergize with antiplatelet compounds, thereby enhancing the ability of endothelial-derived autocoids to inhibit platelet aggregation. The mechanism responsible for this potentiating effect of thiols on platelet aggregation is not known, but may relate to the ability of thiol-containing compounds to act as intracellular scavengers of oxygen-derived free radicals.

Original languageEnglish
Pages (from-to)820-823
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number3
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Pharmacology

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