Affiliation:
1. Department of Cardiovascular and Renal Research Institute of Molecular Medicine, University of Southern Denmark Odense C Denmark
2. Department of Nephrology Odense University Hospital Odense Denmark
Abstract
AbstractAimMagnesium (Mg2+) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium‐derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca2+ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg2+‐dependent vessel relaxation.MethodsTo uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg2+ were studied in intact and endothelium‐denuded aortas. Key findings were confirmed in second‐order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg2+ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine.ResultsMg2+ caused a significant concentration‐dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium‐denuded aortas. The endothelium‐dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg2+ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg2+ augmented acetylcholine‐induced relaxation. SKCa and IKCa channel blockers apamin and TRAM34 inhibited Mg2+‐dependent relaxation. The endothelium‐independent relaxation in aorta rings was inhibited by high extracellular Ca2+. Combined blockade of NO, SKCa, and IKCa channels significantly reduced Mg2+‐dependent dilatation in mesenteric resistance vessels.ConclusionsIn mouse conductance and resistance arteries Mg2+‐induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca2+ in smooth muscle cells, and additional unidentified mechanisms.
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