Dilation and constriction of large coronary arteries in conscious dogs by endothelin

This study examined the effects of endothelin on coronary circulation and the relationship between the plasma concentration of endothelin and cardiovascular function in conscious dogs. The injection of a low dose (50 ng/kg) of endothelin increased coronary artery diameter by 2.17 +/- 0.49% and then decreased coronary artery diameter by 1.13 +/- 0.17% (P less than 0.01) from 3.51 +/- 0.14 mm. This dose increased coronary blood flow by 39 +/- 8.5% and then decreased coronary blood flow by 14 +/- 3.5% (P less than 0.01) from 25 +/- 1.6 ml/min, respectively. Four doses of endothelin (1, 10, 20, and 50 ng.kg-1.min-1) were infused for 20 min each as a cumulative dose response and blood samples were taken to assay endothelin. Significant changes in systemic and coronary dynamics were observed at infusions of 10 and 20 ng.kg-1.min-1. For instance, at 10 ng.kg-1.min-1 there was a significant (P less than 0.05) increase in mean arterial pressure (10 +/- 2.7%), left ventricular (LV) end-diastolic (32 +/- 11%), and LV systolic (8 +/- 3%) pressures and late diastolic coronary resistance (12 +/- 3.0%). This was accompanied by a reduction in large coronary artery diameter (2.0 +/- 0.5%) and coronary blood flow (22 +/- 6.0%; P less than 0.05). At this infusion rate, plasma endothelin reached 70 pg/ml when compared with a control value of 4 +/- 1 pg/ml. Thus the bolus injections of endothelin evoked a biphasic response of large and small coronary arteries, whereas during infusion we observed only vasoconstriction. The levels of circulating endothelin necessary to cause significant cardiovascular effects are much higher than expected.