ABSTRACT
MASAHIKO HIRAFUJI '*, YUKITATSU KANAI', AKI KAWAHARA \ TAKUJIMACHIDA \ NAOYA HAMAUE', HIDEYA SAITO 2 and MASARU MINAMI' 1 Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
2 Department of Basic Sciences, Japanese Red Cross Hokkaido College of Nursing, Kitami, Hokkaido 090-0011, Japan
Abstract-We investigated the effect of 5-hydroxytryptamine (5-HT) on nitric oxide (NO) production by vascular smooth muscle cells derived from 7-8 weeks old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY). 5-HT significantly inhibited NO production and inducible NO synthase (iNOS) expression induced by interleukin-1^ (IL-l/J), which effect was greater in SHRSP cells than in WKY cells. The inhibitory effect of 5-HT was mimicked by a-methyl-5-HT, a 5-HT2 receptor agonist, but not by 5-HT[, 5-HT3 or 5-HT4 receptor agonists. 5-HT inhibition of NO production was dose-dependently reversed by sarpogrelate, a 5-HT2 receptor antagonist. Staurosporin, a protein kinase C (PKC) inhibitor, dose-dependently reversed the inhibitory effect of 5-HT, and phorbol 12-myristate 13-acetate, a PKC activator, dose-dependently inhibited the NO production in both WKY and SHRSP cells. Thus, 5-HT had an inhibitory effect on NO production and iNOS expression by vascular smooth muscle cells via 5-HT2 receptor subtype involving PKC activation, which effect was greater in SHRSP cells than in WKY cells. The enhanced inhibitory effect of 5-HT may have a pathophysiological relevance to vascular diseases in SHRSP.
