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WITHDRAWAL OF MAGNESIUM ENHANCES CORONARY ARTERIAL SPASMS PRODUCED BY VASOACTIVE AGENTS
Author(s) -
ALTURA BURTON M.,
TURLAPATY PRASAD D.M.V.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09343.x
Subject(s) - verapamil , contractility , chemistry , medicine , propranolol , phentolamine , endocrinology , angiotensin ii , methysergide , calcium , receptor , serotonin
1 The influence of external magnesium ions ([Mg 2+ ] o ) on the sensitivity (i.e. EC 50 ) and contractility (maximum response) of isolated large and small coronary arteries of the dog, obtained from different regions of the myocardium, to vasoactive agents was studied. 2 Removal of [Mg 2+ ] o from the physiological salt solution enhanced, while elevation in [Mg 2+ ] o to 4.8 m m , lowered the contractile sensitivity to three different agents, 5‐hydroxytryptamine (5‐HT), angiotensin II and KCl. 3 Contractility, of both large and small coronary arteries, to 5‐HT and angiotensin II was potentiated and depressed, respectively, by withdrawal and elevation of [Mg 2+ ] o ; maximum responses to KCl were not altered by 0 or 4.8 m m [Mg 2+ ] o . 4 Cumulative concentration‐contractile effect curves to CaCl 2 were shifted leftward on removal of [Mg 2+ ] o ; elevation of [Mg 2+ ] o to 4.8 m m shifted the CaCl 2 concentration‐effect curves to the right. Maximal contractile responses to CaCl 2 were enhanced by removal of, and reduced by elevation of, [Mg 2+ ] o5 The calcium 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. 6 A variety of pharmacological antagonists (phentolamine, propranolol, methysergide, atropine, diphenhydramine), as well as use of a prostaglandin cyclo‐oxygenase inhibitor, did not modify the altered contractile responses evoked by angiotensin II or KCl in different concentrations of Mg 2+ . 7 These results suggest: (1) [Mg 2+ ] o may exert considerably greater influence on receptor‐operated rather than membrane‐potential sensitive channels involved in Ca 2+ transport in coronary arterial smooth muscle; (2) Mg 2+ interferes with the affinity (binding) of certain agonists (5‐HT and angiotensin II) for their respective receptors in coronary vascular muscle; and (3) a functional pool of Ca 2+ which is resistant to Ca 2+ ‐depletion, but accessible to activation by 5‐HT and angiotensin II is present in canine coronary arterial smooth muscle.