Effect of cilostazol, a cAMP phosphodiesterase inhibitor, on nitric oxide production by vascular smooth muscle cells

European Journal of Pharmacology
U IkedaK Shimada

Abstract

We investigated the effects of cilostazol, a cAMP phosphodiesterase inhibitor, on nitric oxide (NO) synthesis in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1 beta (10 ng/ml) for 24 h caused a significant increase in the accumulation of nitrite, a stable metabolite of NO. Although cilostazol itself showed no effect on nitrite accumulation, it stimulated interleukin-1 beta-induced nitrite accumulation in a concentration-dependent manner (10(-8)-10(-5) M). This effect of cilostazol was completely abolished in the presence of NG-monomethyl-L-arginine, actinomycin D or dexamethasone. The cilostazol-induced nitrite production was accompanied by increased inducible NO synthase protein expression. In the presence of dibutyryl-cAMP, interleukin-1 beta-induced nitrite accumulation was further increased, but the stimulatory effect of cilostazol on nitrite accumulation was blunted. The effect of cilostazol was also abolished in the presence of Rp-8-bromoadenosine-3',5-cyclic monophosphorothioate, a competitive inhibitor of protein kinase A. Addition of cilostazol to the cultures significantly increased intracellular cAMP levels of vascular smooth muscle cells. These results indicate that cilostaz...Continue Reading

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Citations

Jun 13, 2002·Clinical Cardiology·Arthur M Feldman, Dennis M McNamara
Feb 10, 2009·Surgery Today·Fabio A KudoToshiya Nishibe
Dec 19, 2000·Free Radical Biology & Medicine·D R Janero, J F Ewing
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Jul 21, 2004·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Joong-Seok KimHideki Takami
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Apr 29, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Li-Teh ChangHon-Kan Yip
Apr 27, 2011·Journal of cardiovascular ultrasound·Kyu Seop KimIn-Whan Seong
May 17, 2018·Acta Cirúrgica Brasileira·André PazioGuataçara Schenfelder Salles Junior
Feb 24, 2001·The Annals of Pharmacotherapy·M P Reilly, E R Mohler
Jun 1, 2018·Translational and Clinical Pharmacology·Yun Seob JungKyungsoo Park
Sep 15, 2021·Stroke; a Journal of Cerebral Circulation·Adam de HavenonMaarten G Lansberg
Oct 22, 2021·Journal of Clinical Pharmacology·Antonis A ManolisAntonis S Manolis

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