Coronary responses to endothelin-1 and acetylcholine during partial coronary ischaemia and reperfusion in anaesthetized goats.
To examine coronary reactivity to acetylcholine and endothelin-1 (ET-1) during partial ischaemia and reperfusion, flow in the left circumflex coronary artery was measured electromagnetically, and coronary partial ischaemia was induced by stenosis of this artery in anaesthetized goats. In eight animals not treated with N(G)-nitro-l-arginine methyl ester (l-NAME), coronary stenosis reduced coronary flow by 45%, mean arterial pressure by 16% and coronary vascular conductance by 34%. During this ischaemia, coronary vasodilatation to acetylcholine (0.003-0.1 microg) and sodium nitroprusside (SNP; 1-10 microg) was markedly reduced, and coronary vasoconstriction to ET-1 (0.01-0.3 nmol) was attenuated. After 30 min of reperfusion, coronary flow, mean arterial pressure and coronary vascular conductance remained decreased, and the effects of acetylcholine, SNP and ET-1 were as in control animals. In six goats treated with N(G)-nitro-l-arginine methyl ester, coronary stenosis reduced coronary flow by 26% and coronary vascular conductance by 24%, but did not affect mean arterial pressure. During this ischaemia, coronary vasodilatation to acetylcholine and SNP was also markedly reduced, but vasoconstriction to ET-1 was unaffected. After 30 min of reperfusion, coronary flow and coronary vascular conductance remained decreased and mean arterial pressure was normal; in addition, the effects of acetylcholine were lower, those of SNP were similar and those of ET-1 were higher than in control animals. Therefore partial ischaemia reduces the coronary vasodilator reserve and blunts coronary vasoconstriction to ET-1, and reperfusion does not alter the endothelium-dependent and -independent coronary vasodilatation or vasoconstriction to ET-1.
Departamento de Fisiologi;a, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo 2, 28029 Madrid, Spain.
Maria Angeles
MA
Martínez
Nuria
N
Fernández
Luis
L
Monge
Angel Luis
AL
García-Villalón
Elena
E
Sanz
Godofredo
G
Diéguez
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006041:Goats; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester