Magnesium and blood pressure regulation: systemic and renal mechanisms

Experimental and clinical evidence have demonstrated that Mg deficiency contributes to elevated blood pressure (BP), whereas Mg supplementation exerts modest but consistent antihypertensive effects. The systemic effects of Mg supplementation and/or deficiency on BP have been investigated in relation to vascular smooth muscle cells (VSMCs), the renin-angiotensin-aldosterone system (RAAS), endothelial function, the sympathetic nervous system, and inflammation associated with oxidative stress. Some of these mechanisms are supported by compelling evidence, whereas others remain controversial. In the kidney, following glomerular filtration, ~95% of filtered Mg is reabsorbed along the renal tubules. In the proximal tubule (PT), Mg reabsorption occurs mainly via a paracellular transport pathway driven by a negative transepithelial electrical gradient. In contrast, in the thick ascending limb of Henle's loop (TAL), Mg reabsorption is regulated by electrochemical gradients generated through the coordinated activity of transporters such as the Na-K-2Cl cotransporter (NKCC2) and Na-K-ATPase. In the distal convoluted tubule (DCT), transient receptor potential melastatin 6 and 7 (TRPM6/7) channels tightly regulate the transcellular Mg reabsorption pathway. Hypertension is associated with increased urinary Mg excretion, resulting in relative Mg deficiency. Accumulating evidence suggests that Mg deficiency contributes to the pathogenesis of salt-sensitive and/or implementation hypertension, presumably through mechanisms involving Mg, Na and K transporters, mainly in the TAL and DCT.In this review, we discuss both systemic and renal mechanisms linking Mg to BP regulation. A better understanding of the interactions among Mg, Na, and K transport may provide novel insights into the role of Mg in hypertension. Mg exerts both BP raising and lowering effects depending on the body Mg status. Mg deficiency is associated with increase in BP through the multifaceted systemic and renal mechanisms. Experimental studies have shown that Mg deficiency-induced hypertension can be salt-sensitive and may be associated with implementation hypertension. The pressure-natriuresis curve shifts rightward and downward as salt sensitivity develops, requiring a higher BP to achieve the same level of sodium excretion.