Magnesium sulfate prevents alcohol-induced spasms of cerebral blood vessels: an in situ study on the brain microcirculation from male versus female rats

Abstract

Numerous studies indicate that alcohol can cause neural and vascular damage in the brain. Additional studies indicate that magnesium ions (Mg2+) possess the ability to modify vascular tone. We utilized an image-splitting television microscope recording system in an intact rat brain model in order to determine whether local (topical) application or systemic (intravenous or intra-arterial) administrations of MgSO4 exert vasodilator effects on cerebral arterioles (66-124 microns o.d.) and venules (66-137 microns o.d.). In addition, we investigated whether infusion of low doses of MgSO4 could modify cerebral vascular spasms induced by ethanol and a calcium mimic, i.e., Ba2+. Topical applications of MgSO4 (i.e., 1-100 mumol) in male and female rats produced dose-dependent dilations of cerebral arterioles and venules; male animals were clearly more sensitive to Mg2+. Systemic infusion of low doses of MgSO4 (i.e., 1.0 and 4.0 mumol/min) into the femoral vein or a branch of the internal carotid artery failed, completely, to induce changes in arterial blood pressure or diameter of arterioles and venules. However, such nonvasodilator doses of MgSO4, infused via either route, inhibited contractile responses induced by 5% Ba2+ and 10% ethanol in arterioles and venules in a dose-dependent manner in both male and female rats. Cerebral microvessels of male animals were more sensitive to inhibitory actions of Mg2+ against Ba(2+)-induced microvascular constrictions than were microvessels of females. Administration of a variety of pharmacologic antagonists as well as a cyclo-oxygenase inhibitor failed to influence either the local vasodilator effects of Mg2+ or the inhibitory actions of Mg2+. Basal plasma levels of Mg were higher in female vs. male rats (1.98 +/- 0.06 vs. 1.77 +/- 0.028 mg/dl). Systemic administration of MgSO4 in cerebral nonvasodilator doses resulted in rapid elevation of plasma Mg levels in a dose-dependent manner (e.g., 0.3-4.3 mg/dl over control levels). Plasma Mg levels were more elevated in female than male animals. It is concluded that magnesium ions can act as local vasodilators, in physiologic doses, on brain microvessels and that these divalent cations possess antispasmodic activities, in nonvasodilator doses, on intact rat brain arterioles and venules. In addition, our findings suggest that Mg2+ might be useful in the treatment and prevention of alcohol-induced brain vascular damage.