Endothelin blockade lowers total peripheral resistance in hemorrhagic shock recovery

Abstract

To determine whether endothelin (ET) has a role in maintaining circulatory support during hypotensive hemorrhage, we (1) examined cardiac and systemic hemodynamics after a 6-mL hemorrhage in the presence and absence of the ET(A) receptor blocker BQ-123, (2) examined cardiac and systemic hemodynamics during BQ-123 infusion in nonhemorrhaged rats, (3) measured changes in circulating immunoreactive endothelin (IR-ET) after a 6-mL hemorrhage, and (4) infused pathophysiological doses of ET-1 into rats anesthetized with thiobutabarbital. Twenty minutes after hemorrhage, cardiac output and mean arterial pressure had stabilized in part because of an increase in systemic vascular resistance from 0.86±0.04 (baseline) to 1.04±0.05 (20 minutes) mm Hg/mL per minute. The rise in systemic vascular resistance was temporally associated with a significant (24%) increase in circulating IR-ET from 29±2 to 36±3 pg/mL 20 minutes after hemorrhage. During BQ-123 infusion mean arterial pressure at 5, 10, and 20 minutes after hemorrhage was 9±2, 23±4, and 23±3 mm Hg lower than values obtained after hemorrhage alone (P