Inhibitory effect of melatonin on α1-adrenergic–induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats

• Published in: American journal of hypertension 2004-04, Vol.17 (4), p.339-346
• Main Authors: Girouard, Hélène, Champlain, Jacques de
• Format: Article
• Language: English
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Medical sciences; Melatonin; mesenteric artery; spontaneously hypertensive rats; superoxide anion; α1-adrenergic pathway
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/j.amjhyper.2003.12.013

Background: The aim of this study was to assess the effects of melatonin on α1-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 α1-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 α1-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.