New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system. II. Experimental aspects.

It has generally been believed that the physiological roles for magnesium ions (Mg2+) in cardiac and vascular smooth muscle are limited to regulation of contractile proteins, sarcoplasmic reticular membrane transport of calcium ions (Ca2+), cofactor in ATPase activities and metabolic regulation of energy-dependent cytoplasmic and mitochondrial pathways. In addition, up until recently, it was not thought that small changes in free external ([Mg2+]0) or cytoplasmic Mg2+ could exert any significant effects on cardiac or vascular smooth muscle contractility. It is clear, however, from the newer studies that [Mg2+]0 can affect tension and contractility of these muscle cells by altering membrane and intracellular organelle binding and transport of Ca2+, affecting hormone-receptor interactions, regulating electrolyte content and transport, affecting resting membrane-generated and action potentials, altering excitation-contraction coupling events, and regulate peripheral and cerebral vascular tone and blood flow. In addition, it is also now clear that small changes of free [Mg2+] at the cardiac and vascular muscle membranes can exert significant effects on mechanical and electrical activities of these cells. Considerable new data lend support to the idea that [Mg2+]0 is fundamental in the regulation of cardiovascular homeostasis. Dietary, metabolic or drug-induced changes in Mg2+ levels appear to play important roles in the etiology of cardiac and vascular disorders. Evidence is reviewed and presented to indicate that Mg2+ is important in the pathophysiology and treatment of certain forms of experimental and genetic types of hypertension. This divalent cation may also be important in the etiology of a variety of disorders which have vasospasm in common. Evidence is reviewed to support the concept that Mg2+ is a naturally occurring or mimic weak Ca2+ antagonist, which should be useful in the treatment of several types of cardiac and vascular disorders.