Mode of action of ergonovine on isolated porcine coronary artery: the role of Ca2+.
Coronary vasoconstrictor responses to ergonovine were examined in helical coronary arterial strips of young swine. Both ergonovine and serotonin (5-hydroxytryptamine) produced dose-dependent contractions of the strips. The distal region (less than 1.00 mm outer diameter) of the circumflex coronary artery was most sensitive to the responses of serotonin and ergonovine. Methysergide and nifedipine significantly depressed the contractions induced by ergonovine and serotonin. Atropine, propranolol, and the alpha 1 blocker, prazosin, did not antagonize ergonovine-induced contractions. The ergonovine response may depend entirely upon extracellular Ca2+ while the effect of serotonin may be mediated in part through the mobilization of intracellular Ca2+ stores. Increases in 45Ca2+ cellular contents occurred after ergonovine or serotonin and these increases were blocked by methysergide or nifedipine at concentrations which blocked mechanical responses to the agonist. It is concluded that the contractions of the porcine coronary artery produced by ergonovine and serotonin are as follows: (i) regionally sensitive; (ii) blocked by Ca2+ antagonists and therefore may utilize Ca2+ channels similar to those described in other excitable tissues; (iii) blocked by methysergide. These studies indicate that the major mechanism of ergonovine's action in the porcine coronary artery is through the activation of serotonin receptors on coronary arteries which are, in turn, linked to Ca2+ channels. However, this mechanism of action may be different in an intact animal.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004874:Ergonovine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D012701:Serotonin; D009543:Nifedipine; D002118:Calcium; D004874:Ergonovine; D008784:Methysergide