Mechanisms of the ergonovine-induced vasoconstriction in the rabbit main coronary artery.
The mean membrane potential of smooth muscle cells of the rabbit main coronary artery was -60.3 mV and an evoked action potential could be recorded in response to acetylcholine (ACh). Ergonovine or 5-hydroxytryptamine (5-HT) slightly depolarized the membrane and methysergide, a relatively selective antagonist for the 5-HT receptor, had a slight inhibitory action on these depolarizations. 5-HT produced larger contractions than ergonovine, and the concentration-effect relationships obtained for both agents shifted to higher concentrations following pre-equilibration with methysergide. ACh (10(-11)M) slightly hyperpolarized the membrane and relaxed the tissue, and high concentrations of ACh (greater than 10(-8)M) depolarized the membrane, increased the membrane resistance and produced a contraction. ACh but not ergonovine or 5-HT, produced a contraction in Ca-free EGTA-containing solution. Following a 60 min pre-equilibration with indomethacin, the ergonovine-induced contraction was markedly enhanced but the 5-HT- or ACh-induced contractions were not. Removal of the endothelium by rubbing the vascular lumen enhanced the ergonovine- or ACh-induced contractions, but not those to 5-HT. The results obtained can be summarized as follows: ergonovine probably accelerates Ca influx and thereby produces contraction in the rabbit main coronary artery. This contraction is due to activation of the 5-HT receptor as an agonist, but the ergonovine-induced contraction is attenuated due to activation of the endothelium from which inhibitory prostanoid substances may be released. Ergonovine, therefore, may produce greater contractions in coronary arteries with damaged endothelium than in intact tissues.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D004874:Ergonovine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D011448:Prostaglandin Antagonists; D012701:Serotonin; D000109:Acetylcholine; D004874:Ergonovine; D007213:Indomethacin