Hemodynamic effects of a selective endothelin--a receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats.

The time-course changes in blood pressure (BP), cardiac output (CO), and total peripheral conductance (TPC) were investigated during a bolus i.v. infusion of BMS-182874, a selective ETA receptor antagonist, in conscious, unrestrained DOCA-salt hypertensive rats and Sham-operated control rats (SHAM). BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time flow probes. In contrast to vehicle-treated controls, BMS-182874 reduced BP and increased TPC in DOCA-salt hypertensive rats but not in SHAM-rats. A small increase in CO tended to oppose the BP-lowering effect of the antagonist. The results suggest that the role of ETA receptors in the maintenance of the hypertensive state in the DOCA-salt model of hypertension is exerted at the level of the resistance vessels and not on factors that regulate CO.