title: Withdrawal of magnesium enhances coronary arterial spasms produced by vasoactive agents.
abstract: 1 The influence of external magnesium ions ([Mg2+]o) on the sensitivity (i.e. EC50) 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 [Mg2+]o from the physiological salt solution enhanced, while elevation in [Mg2+]o to 4.8 mM, 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 [Mg2+]o; maximum responses to KCl were not altered by 0 or 4.8 mM [Mg2+]o. 4 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. 5 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 Mg2+. 7 These results suggest: (1) [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; (2) Mg2+ 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 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.
mesh_terms: D000802:Angiotensin Amide / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000804:Angiotensin II; D012701:Serotonin; D000802:Angiotensin Amide; D014700:Verapamil; D008274:Magnesium; D011188:Potassium