Inhibitory effect of melatonin on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats.
BACKGROUND
The aim of this study was to assess the effects of melatonin on alpha1-adrenergic pathway in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.


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 alpha1-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 alpha1-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.
Girouard
Hélène
H
Research Group on Autonomic Nervous System, Department of Physiology, Faculty of Medicine, University of Montréal, Montréal, Québec, Canada.
de Champlain
Jacques
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007295:Inositol Phosphates / Q000378:metabolism; D008550:Melatonin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013152:Splanchnic Circulation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000975:Antioxidants; D007295:Inositol Phosphates; D013481:Superoxides; D010656:Phenylephrine; D013482:Superoxide Dismutase; D008550:Melatonin