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Enhanced inhibitory effect of 5-hydroxytryptamine on nitric oxide production by vascular smooth muscle cells derived from stroke-prone spontaneously hypertensive rats

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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-1β (IL-1β), which effect was greater in SHRSP cells than in WKY cells. The inhibitory effect of 5-HT was mimicked by α-methyl-5-HT, a 5-HT2 receptor agonist, but not by 5-HT1, 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.

10.1163/1569391041501942
/content/journals/10.1163/1569391041501942
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/content/journals/10.1163/1569391041501942
2004-06-01
2016-12-06

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