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  • Title: Microcirculatory actions and uses of naturally-occurring (magnesium) and novel synthetic calcium channel blockers.
    Author: Altura BM, Altura BT.
    Journal: Microcirc Endothelium Lymphatics; 1984 Apr; 1(2):185-220. PubMed ID: 6400430.
    Abstract:
    Synthetic calcium channel blockers (Ca2+ entry blockers or antagonists) have been reported to induce relaxation of smooth muscle which is not thought to be mediated by any specific action(s) on receptor sites. In addition, it has been suggested that Ca2+ channel blockers increases blood flow in a number of organ regions, including mesenteric, femoral, renal, cerebral and coronary vasculatures, via a direct action on vascular tone by inhibiting Ca2+ influx across the vascular smooth muscle membranes. Such information has prompted clinical studies with the use of Ca2+ channel blockers in the treatment of a wide variety of cardiovascular disorders. The questions, to be answered, however, are whether any of the newly-designed channel blockers can actively produce vasodilatation of arterioles and venules in regional microvasculatures, and these synthetic agents are safe and therapeutically effective. In addition, can one design site-specific (e.g., cerebral vs. coronary vasodilator) Ca2+ channel blockers. But, since the body has a natural Ca2+ antagonist, viz., magnesium ions (Mg2+), one must ask whether such divalent cations act as peripheral vasodilators and are effective as therapeutic agents. The studies reviewed herein: compare the effects of several different Ca2+ channel blockers on resistance and capacitance vessels in different regional microvasculatures (i.e., mesenteric, skeletal muscle, pial) within a single species, namely the rat, by high-resolution TV microscopy, and demonstrate the rationale, effects and mechanisms of action of Mg2+ on regional blood vessels. These data show some of the new, novel synthetic Ca2+ channel blockers (i.e., nisoldipine, nitrendipine, nimodipine) can: exert effects on both arterioles and venules in certain vasculatures; be designed to exert a wide range of potencies; and be designed to act selectively at regional microvasculatures. In addition, the data presented are consistent with the hypothesis that Mg2+ exerts a regulatory role in vascular tone, vascular reactivity and vascular resistance. Certain vascular diseases associated with a Mg2+-deficiency appear to be amenable to treatment with Mg2+.
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