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The relative contribution of cardiac output (CO) and total peripheral conductance (TPC) to the changes in blood pressure (BP) evoked by an intravenous injection of bosentan, a nonpeptide mixed endothelin (ET) antagonist, were investigated in conscious unrestrained deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham-control rats. Blood pressure was recorded by radiotelemetry devices and CO by ultrasonic transit-time flow probes. Bosentan significantly reduced BP (from 141 +/- 3 to 111 +/- 3 mm Hg) and increased TPC (from 1.19 +/-0.1 to 1.72 +/- 0.2 mL/min/kg/mm Hg) in DOCA-salt hypertensive rats, but not in sham rats. An increase in CO opposed the BP-lowering effect of the antagonist. The results demonstrate that the role of ET 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 cardiac output.

american journal of hypertension

Total peripheral conductance mediates antihypertensive effect of nonpeptide mixed endothelin receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats