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 µ g) and sodium nitroprusside (SNP; 1–10 µ g) was markedly reduced, and coronary vasoconstriction to ET-1 (0.01–0.3nmol) was attenuated. After 30min 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 30min 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.

The coronary effects of endothelin-1 (ET-1) during acute hypertension were examined in anesthetized goats, where the left circumflex coronary artery flow was electromagnetically measured and hypertension was induced by constriction of the thoracic aorta. In six non-treated goats, aortic constriction increased arterial pressure (mean arterial pressure = 128±5mmHg) and coronary flow (by 34%) without changing coronary vascular conductance. In this case, ET-1 (0.01–0.3nmol) when injected intracoronarily, decreased coronary vascular conductance, which was similar in hypertension and in normotension. In eight N G -nitro-L-arginine methyl ester-treated goats, aortic constriction increased arterial pressure (mean arterial pressure = 131±5mmHg) and coronary flow (by 26%) and decreased coronary vascular conductance (by 17%). In this case, ET-1 (0.01–0.3nmol) also decreased coronary vascular conductance, which was similar in N G -nitro-L-arginine methyl ester-treated hypertension that observed in normotension. Therefore, acute hypertension attenuates the coronary vasoconstriction caused by ET-1, and this attenuation might be related to mechanisms other than changes in NO release.

The aim of this study was to analyse the modulatory role of endothelin-1 and vasopressin in sympathetic vasoconstriction, and whether there are gender differences in this modulatory role. Electrical field stimulation (4Hz, 0.2ms pulse duration at supramaximal voltage of 70V, for 1s), applied to isolated segments from rat tail arteries, produced a contraction that was lower in the vascular segments from female than in those from male rats. This arterial contraction was potentiated in a concentration-dependent way by endothelin-1 (10 -10 –3×10 -9 mol/l) and vasopressin (10 -12 –10 -10 mol/l), and the increment produced by endothelin-1 was similar in the arteries of both, whereas the increment induced by vasopressin was higher in the arteries from male than in those from female rats. These results suggest that endothelin-1 and vasopressin potentiate the vasoconstriction to sympathetic stimulation, and this potentiating effect of vasopressin may be higher, whereas that of endothelin-1 may be similar, in males than in females.