Mg²⁺–Ca²⁺ interaction in contractility of vascular smooth muscle: Mg²⁺ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels

Abstract

Contractility of all types of invertebrate and vertebrate muscle is dependent upon the actions and interactions of two divalent cations, viz, calcium (Ca2+) and magnesium (Mg2+) ions. The data presented and reviewed herein contrast the actions of several organic Ca2+ channel blockers with the natural, physiologic (inorganic) Ca2+ antagonist, Mg2+, on microvascular and macrovascular smooth muscles. Both direct in vivo studies on microscopic arteriolar and venular smooth muscles and in vitro studies on different types of blood vessels are presented. It is clear from the studies done so far that of all Ca2+ antagonists examined, only Mg2+ has the capability to inhibit myogenic, basal, and hormonal-induced vascular tone in all types of vascular smooth muscle. Data obtained with verapamil, nimopidine, nitrendipine, and nisoldipine on the microvasculature are suggestive of the probability that a heterogeneity of Ca2+ channels, and of Ca2+ binding sites, exists in different microvascular smooth muscles; although some appear to be voltage operated and others, receptor operated, they are probably heterogeneous in composition from one vascular region to another. Mg2+ appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. The organic Ca2+ channel blockers do not have this uniform capability; they demonstrate a selectivity when compared with Mg2+. Mg2+ appears to be a special kind of Ca2+ channel antagonist in vascular smooth muscle. At vascular membranes it can (i) block Ca2+ entry and exit, (ii) lower peripheral and cerebral vascular resistance, (iii) relieve cerebral, coronary, and peripheral vasospasm, and (iv) lower arterial blood pressure. At micromolar concentrations (i.e., 10-100 microM). Mg2+ can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mg2+ is three to five orders of magnitude less potent than the organic Ca2+ channel blockers, it possesses unique and potentially useful Ca2+ antagonistic properties.

Effects of Folic Acid and Magnesium on the Production of Homocysteine-Induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle Cells

“…34 Magnesium, a natural calcium antagonist, acts on potential-operated channels, receptor-operated channels, and leak-operated channels in the cardiovascular system. 35 We previously reported the effects of magnesium on the production of extracellular MMPs in cultured rat VSMCs, 36 and recently, magnesium has been shown to inhibit capacitative Ca 2+ entry in VSMCs. 37 Li et al suggested the need for the 3 B-vitamins (folic acid, vitamin B6 and B12), together with normal physiological levels of magnesium, in order to prevent [Mg 2+ ]I depletion and occlusive cerebral diseases induced by hyperhomocysteinemia.…”

The effect of lowering blood pressure by magnesium supplementation in diabetic hypertensive adults with low serum magnesium levels: a randomized, double-blind, placebo-controlled clinical trial

“…27 Among these, it has been reported that magnesium inhibits the effect of calcium from vascular smooth muscle sarcoplasmic reticulum by competition for a calcium receptor on a calcium-regulated efflux channel, 28 essentially acting as a calcium blocker. Recently, two cation channels of the transient receptor potential melastatin cation channel family have been identified as magnesium transporters and implicated as a signalling kinase involved in vascular smooth muscle cell growth, apoptosis, adhesion, contraction, cytoskeleton organization and migration, as well as important processes involved in vascular remodelling associated with hypertension and other vascular diseases.…”

Mechanisms of the Enhanced Contractile Response to Phenylephrine in Thoracic Aorta Isolated from Rats with Dietary Magnesium Deficiency

“…It is well known that magnesium ions (Mg2+) influence the contractile response of isolated blood vessels to some endogenous vasoactive agents such as norepinephrine and serotonin (1). These experiments showed that low concen trations of Mg2+ in physiological salt solution enhance Ca2+-entry into smooth muscle cells, resulting in en hanced muscular contraction.…”