Mg²⁺-induced endothelium-dependent relaxation of blood vessels and blood pressure lowering: role of NO

Abstract

In vitro extracellular Mg(2+) concentration ([Mg(2+)](0)) produces endothelium-dependent and endothelium-independent relaxations in rat aorta in a concentration-dependent manner. These relaxant effects of Mg(2+) 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. [Mg(2+)](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 Ca(2+) concentration ([Ca(2+)](0)) or buffering intracellular Ca(2+) concentration in endothelial cells, with 10 microM 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, markedly attenuated the relaxant effects of Mg(2+). Mg(2+) produced nitric oxide (NO) release from the intact aortic rings in a concentration-dependent manner. Removal of [Ca(2+)](0) diminished the increased NO release induced by elevated levels of [Mg(2+)](0). In vivo infusion of increasing doses (1-30 microM/min) of MgSO(4), 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 MgSO(4), intravenous administration of either L-NMMA (10 mg/kg) or L-NAME (10 mg/kg) increased (i.e., reversed) the MgSO(4)-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 Mg(2+) dilatations and 2) the endothelium-dependent relaxation induced by extracellular Mg(2+) is mediated by release of endothelium-derived relaxing factor-NO from the endothelium, and requires Ca(2+) and formation of guanosine 3',5'-cyclic monophosphate.

Relation of Cellular Potassium to Other Mineral Ions in Hypertension and Diabetes

“…Indeed, cellular depletion of K i and Mg i is associated with elevated blood lipid levels, atherosclerosis, 32 altered endothelial function, and decreased biosynthesis and release of NO. 33 Second, the coordinate nature of these cellular ionic lesions-ie, abnormal levels of any 1 ion reflecting linked abnormalities of others-suggests the somewhat artificial nature of controversies arising out of claims that 1 particular cellular ionic species is more important than another. It may be rather, that independently of the nature of the initial lesion, which might differ in different genetically or environmentally determined forms of hypertension and/or diabetes (and which may or may not involve primary ion-related events), that the alterations of cellular ion content observed here participate in a final common pathway necessary for the emergence of the insulin resistant and/or hypertensive state.…”

A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children

“…[11][12][13][14][15] Magnesium, a known vasodilator with anti-inflammatory effects, has the potential to alter the pathophysiology of pain crises. [16][17][18][19][20] In addition to work exploring the use of magnesium administered orally to prevent pain crises, 21,22 2 previous single-institution studies examining the effects of IV magnesium on acute pain crisis yielded conflicting results: one showed a shortened length of stay (LOS) from a median of 5 days to a median of 3 days compared with previous hospitalizations by the same individuals. Conversely, a randomized trial conducted in Canada with 104 children and an average LOS of more than 5 days found no decrease in length of hospitalization.…”

Magnesium: Effect on ocular health as a calcium channel antagonist

“…Magnesium therapy may also improve endothelial function [12,13]. In addition to reverse interaction with ET-1, magnesium induces endothelium-dependent vasodilation mediated by endothelial NO [9,10]. NO, derived from nitric oxide synthase-3 in vascular endothelium, contributes to regulation of local circulatory disturbances, and may be neuroprotective by causing vasodilation and increased blood flow in the glaucoma patients [59,60].…”

“…Elevated magnesium levels prevents ET-1 induced contractile responses by inhibition of ET-1's production and its hypertrophic effect [7,8]. Endothelium-dependent vasodilation mediated by NO is induced with magnesium by modifying formation and release of NO [9][10][11]. Indeed, magnesium therapy may improve endothelial function in patients with diabetes and coronary artery diseases [12,13].…”