Enhanced nitric oxide and cyclic GMP formation plays a role in the anti-platelet activity of simvastatin

T. C. Chou, Y. F. Lin, W. C. Wu, K. M. Chu

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)

摘要

Background and purpose: It has been found that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert various vascular protective effects, beyond their cholesterol-lowering property, including inhibition of platelet-dependent thrombus formation. The objective of the present study was to determine whether the nitric oxide (NO)/cyclic GMP-mediated processes in platelets contribute to the anti-aggregatory activity of simvastatin. Experimental approach: After rabbit platelets were incubated with simvastatin for 5 min, aggregation was induced and the platelet aggregation, nitric oxide synthase activity, guanylyl cyclase activity, NO and cyclic GMP formation were measured appropriately. Key results: Treatment with simvastatin concentration-dependently inhibited platelet aggregation induced by collagen or arachidonic acid with an IC 50 range of 52-158 μM. We also demonstrated that simvastatin (20-80 μM) concentration-dependently further enhanced collagen-induced NO and cyclic GMP formation through increasing NOS activity (from 2.64±0.12 to 3.52±0.21-5.10±0.14 μmol min -1 mg protein -1) and guanylyl cyclase activity (from 142.9±7.2 to 163.5±17.5-283.8±19.5 pmol min -1 mg protein -1) in the platelets. On the contrary, inhibition of platelet aggregation by simvastatin was markedly attenuated (by about 50%) by addition of a nitric oxide synthase inhibitor, a NO scavenger or a NO-sensitive guanylyl cyclase inhibitor. The anti-aggregatory effects of simvastatin were significantly increased by addition of a selective inhibitor of cyclic GMP phosphodiesterase. Conclusions and implications: Our findings indicate that enhancement of a NO/cyclic GMP-mediated process plays an important role in the anti-aggregatory activity of simvastatin.

原文英語
頁(從 - 到)1281-1287
頁數7
期刊British Journal of Pharmacology
153
發行號6
DOIs
出版狀態已發佈 - 3月 2008
對外發佈

ASJC Scopus subject areas

  • 藥理

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