Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels. (October 2017)

• Record Type: Journal Article
• Authors: Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L
• Is Part Of: Journal of molecular endocrinology. Volume 59:Number 3(2017)
• Page Start: 219
• Page End: 233
• Publication Date: 2017-10
• Subjects: melatonin -- BKCa channels -- mesenteric artery -- vascular smooth muscle cell; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-17-0028
• Languages: English
• ISSNs: 0952-5041

Abstract

Abstract : Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BKCa ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BKCa channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l -arginine methyl ester (l -NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC50 . The effect of melatonin was significantly attenuated in the presence of BKCa channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+)l -NAME and (−)l -NAME groups. In the (+)l -NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration–relaxation curve, with pIC50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BKCa channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BKCa channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BKCa channels on mesenteric arterial myocytes.