Mg2+-induced endothelium-dependent relaxation of blood vessels and blood pressure lowering: role of NO
In vitro extracellular Mg2+ concentration ([Mg2+]0) produces endothelium-dependent and endothelium-independent relaxations in rat aorta in a concentration-dependent manner. These relaxant effects of Mg2+ on intact rat aortic rings, but not denuded rat aortic rings, were suppressed by either N G-monomethyl-l-arginine (l-NMMA), N ω-nitro-l-arginine methyl ester (l-NAME), or methylene blue. The inhibitory effects of l-NMMA and l-NAME could be reversed partly by l-arginine. [Mg2+]0-induced dilatation in vivo in rat mesenteric arterioles and venules was almost completely inhibited by N G-nitro-l-arginine andl-NMMA. Removal of extracellular Ca2+concentration ([Ca2+]0) or buffering intracellular Ca2+ concentration in endothelial cells, with 10 μM 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM, markedly attenuated the relaxant effects of Mg2+. Mg2+ produced nitric oxide (NO) release from the intact aortic rings in a concentration-dependent manner. Removal of [Ca2+]0 diminished the increased NO release induced by elevated levels of [Mg2+]0. In vivo infusion of increasing doses (1–30 μM/min) of MgSO4, directly into the femoral veins of anesthetized rats, elicited significant concentration-dependent sustained increases in serum total Mg and concomitant decreases in arterial blood pressure. Before and after employment of various doses of MgSO4, intravenous administration of either l-NMMA (10 mg/kg) orl-NAME (10 mg/kg) increased (i.e., reversed) the MgSO4-lowered blood pressure markedly, and intravenous injection of l-arginine restored partially the increased blood pressure effects of both l-NMMA andl-NAME. Our results suggest that 1) small blood vessels are very dependent on NO release for Mg2+dilatations and 2) the endothelium-dependent relaxation induced by extracellular Mg2+ is mediated by release of endothelium-derived relaxing factor-NO from the endothelium, and requires Ca2+ and formation of guanosine 3′,5′-cyclic monophosphate.