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-omega-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 and L-NMMA. Removal of extracellular Ca2+ concentration ([Ca2+](0)) or buffering intracellular Ca2+ concentration in endothelial cells, with 10 mu M 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 mu M/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) or L-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 and L-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.