期刊
AMERICAN JOURNAL OF HYPERTENSION
卷 17, 期 4, 页码 339-346出版社
OXFORD UNIV PRESS
DOI: 10.1016/j.amjhyper.2003.12.013
关键词
melatonin; alpha-adrenergic pathway; spontaneously hypertensive rats; mesenteric artery; superoxide anion
Background: The aim of this study was to assess the effects of melatonin on alpha(1)-adrenergic pathway in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Methods and Results: The SHR are characterized by a higher vasoconstriction (P < .001) and inositol phosphate formation (P < .001) in response to phenylephrine (PHE) and an increased superoxide anion production (P < .001) in mesenteric arteries. Melatonin and 2-iodomelatonin produced a significant inhibition of the PHE-induced vasoconstriction in isolated and perfused mesenteric beds (P < .001) with the same magnitude in SHR and WKY rats. Melatonin significantly decreased the inositol phosphate (IPs) formation in isolated mesenteric arteries from SHR compared to WKY rats (P < .001). The inhibitory effect of melatonin was increased by the removal of endothelium (P < .001). No effects of superoxide dismutase (SOD), tempol, or catalase were observed on the PHE-induced vasoconstriction. Moreover, no superoxide anion scavenging effect of 2-iodomelatonin was observed in isolated mesenteric vascular muscle cells using lucigenin. Conclusions: The present study showed that high melatonin concentrations inhibit the alpha(1)-adrenergic-induced vasoconstriction and inositol phosphate formation in mesenteric arteries from SHR and WKY rats. The vasorelaxant effect of the melatonin receptors agonist, 2-iodomelatonin, and the absence of any vasoactive effect of antioxidants such as SOD, tempol, and catalase suggest that melatonin exerts its inhibition on alpha(1)-adrenergic-induced vasoconstriction of mesenteric arteries through a low-affinity membrane receptor negatively coupled to the IPs formation and that this effect is independent of its antioxidant properties. (C) 2004 American Journal of Hypertension, Ltd.
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