The mechanism of ergometrine-induced coronary arterial spasm: in vitro studies on canine arteries.
The mechanism by which ergometrine provokes coronary vasospasm was investigated in vitro. Changes in tension were monitored isometrically on spiral strips of freshly obtained coronary (ventricular and circumflex branches) and basilar arteries from dogs. Cumulative concentration-response curves were established for noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT), and ergometrine. The catecholamines either contracted or relaxed the coronary vascular smooth muscle by stimulating alpha- or beta-adrenoceptors, respectively, whereas both 5-HT and ergometrine consistently induced contraction of coronary arteries. In order to antagonize ergometrine-induced contraction on circumflex coronary arteries, appromimately 60-fold greater concentrations of phentolamine were required compared to those necessary for antagonism of noradrenaline. The concentration-response curve for noradrenaline was unchanged by ergometrine, indicating that the two compounds combine with different receptors. The use of the antagonists phentolamine, indoramine, pimozide, pizotifen, and methysergide provided evidence that ergometrine and 5-HT induce contraction of coronary arteries by stimulating the same type of 5-HT receptor, which, however, seems to be different from the 5-HT receptor present in basilar arteries. It is suggested that in Prinzmetal's variant form of angina, ergometrine can provoke coronary vasospasm by increasing the tone of the coronary vascular smooth muscle via stimulation of 5-HT receptors, thus reinforcing sympathetic coronary vascular tone.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004874:Ergonovine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects
D011985:Receptors, Serotonin; D004874:Ergonovine