Abstract
Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 microM) potentiated NO production triggered by IL-1beta. The mRNA and protein expression of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor of protein kinase A, and N(G)-monomethyl-L-arginine, an inhibitor of NO synthase, abrogated cilostazol-enhanced IL-1beta-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1beta-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway.
MeSH terms
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Animals
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Apoptosis*
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Cells, Cultured
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Cilostazol
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Cyclic AMP-Dependent Protein Kinase Type II
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Cyclic AMP-Dependent Protein Kinases / physiology
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Dose-Response Relationship, Drug
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Drug Synergism
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Interleukin-1 / pharmacology*
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Kinetics
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Male
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / enzymology
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Muscle, Smooth, Vascular / metabolism*
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Nitrites / analysis
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Phosphodiesterase Inhibitors / pharmacology*
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Signal Transduction
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Tetrazoles / pharmacology*
Substances
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Interleukin-1
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Nitrites
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Phosphodiesterase Inhibitors
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RNA, Messenger
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Tetrazoles
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Nitric Oxide
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Cyclic AMP-Dependent Protein Kinase Type II
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Cyclic AMP-Dependent Protein Kinases
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Cilostazol