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 μM), 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.