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Nitric oxide (NO) inhibits platelet aggregation primarily via a cyclic 3'5'-guanosine monophosphate (cGMP)-dependent process. Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor that potentiates NO action by reducing cGMP breakdown. We hypothesised that sildenafil would augment the inhibitory effects of NO on in vitro platelet aggregation. After incubation with sildenafil or the soluble guanylate cyclase inhibitor H-(1,2,4)oxadiazolo(4,3-a)quinoxallin-1-one (ODQ), collagen-mediated human platelet aggregation was assessed in the presence of two NO donors, the cGMP-dependent sodium nitroprusside (SNP) and the cGMP-independent diethylamine diazeniumdiolate (DEA/NO). SNP and DEA/NO caused a concentration-dependent inhibition of platelet aggregation. ODQ inhibited and sildenafil augmented the effect of SNP, and to a lesser extent the effect of DEA/NO. We conclude that sildenafil potentiates NO-mediated inhibition of platelet aggregation through blockade of cGMP metabolism and that PDE5 inhibitors may have important antiplatelet actions relevant to the prevention of cardiovascular disease.

Original publication

DOI

10.1016/j.bbrc.2005.09.060

Type

Journal

Biochem biophys res commun

Publication Date

11/11/2005

Volume

337

Pages

382 - 385

Keywords

3',5'-Cyclic-GMP Phosphodiesterases, Azo Compounds, Cyclic GMP, Cyclic Nucleotide Phosphodiesterases, Type 5, Diethylamines, Drug Synergism, Humans, Nitric Oxide, Nitric Oxide Donors, Nitroprusside, Phosphodiesterase Inhibitors, Piperazines, Platelet Aggregation, Platelet Aggregation Inhibitors, Purines, Sildenafil Citrate, Sulfones