WITHDRAWAL OF MAGNESIUM ENHANCES CORONARY ARTERIAL SPASMS PRODUCED BY VASOACTIVE AGENTS

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Abstract
The influence of external magnesium ions ([Mg2+]o) on the sensitivity (i.e., EC50 [median effective concentration]) and contractility (maximum response) of isolated large and small coronary arteries of the dog, obtained from different regions of the myocardium, to vascoactive agents were studied. Removal of [Mg2+]o from the physiological salt solution enhanced, while elevation in [Mg2+]o to 4.8 mM, lowered the contractile sensitivity to 3 different agents, 5-hydroxytryptamine (5-HT), angiotensin II and KCl. Contractility, of both large and small coronary arteries, to 5-HT and angiotensin II was potentiated and depressed, respectively, by withdrawal and elevation of [Mg2+]o; maximum responses to KCl were not altered by 0 or 4.8 mM [Mg2+]o. Cumulative concentration-contractile effect curves to CaCl2 were shifted leftward on removal of [Mg2+]o; elevation of [Mg2+]o to 4.8 mM shifted the CaCl2 concentration-effect curves to the right. Maximal contractile responses to CaCl2 were enhanced by removal of, and reduced by elevation of, [Mg2+]o. The Ca channel blocking agent, verapamil (10-6 M), inhibited completely contractile responses to KCl; contractile responses elicited by angiotensin II and 5-HT were attenuated by verapamil. A variety of pharmacological antagonists (phentolamine, propranolol, methysergide, atropine and diphenhydramine), as well as use of a prostaglandin cyclo-oxygenase inhibitor [indomethacin], did not modify the altered contractile responses evoked by angiotensin II or KCl in different concentrations of Mg2+. These results suggest the following: [Mg2+]o may exert considerably greater influence on receptor-operated rather than membrane-potential sensitive channels involved in Ca2+ transport in coronary arterial smooth muscle; Mg2+ interferes with the affinity (binding) of certain agonists (5-HT and angiotensin II) for their respective receptors in coronary vascular muscle; and a functional pool of Ca2+ which is resistant to Ca2+-depletion, but accessible to activation by 5-HT and angiotensin II is present in canine coronary arterial smooth muscle.