Regional hemodynamic effects of endothelin-1 in conscious, unrestrained, Wistar rats

Regional hemodynamic measurements were made in conscious, unrestrained, Wistar rats chronically instrumented with pulsed Doppler flow probes around left renal and superior mesenteric arteries and the distal abdominal aorta, or around left and right common carotid arteries. The cardiovascular changes with i.v. bolus doses (0.004 and 0.04 nmol) or a 20-min infusion (0.04 nmol/20 min of endothelin-1 (ET-1) were assessed. ET-1 at a dose of 0.004 nmol had no effect on mean arterial pressure (MAP), but caused reductions in renal and mesenteric blood flow accompanied by hindquarters hyperemia; there were no changes in carotid hemodynamics. The higher bolus dose (0.04 nmol) of ET-1 caused initial hypotension and tachycardia followed by hypertension and bradycardia; these changes were associated with sustained reductions in renal and mesenteric flows but a transient hindquarters hyperemia. There was an initial carotid hyperemia followed by a marked reduction in blood flow. Infusion of ET-1 caused progressive bradycardia and hypertension accompanied by reductions in renal and mesenteric flows, but no changes in hindquarters or carotid hemodynamics. These observations are consistent with the hyperemia in the latter vascular beds with high bolus doses of ET-1 due to release of an endogenous vasodilator substance(s).