Endothelin blockade lowers total peripheral resistance in hemorrhagic shock recovery.
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 ETA 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 < .05). Mean arterial pressure was unaffected by BQ-123 infusion at baseline and 30 minutes after hemorrhage. Systemic vascular resistance was not affected at baseline by BQ-123 infusion. However, systemic vascular resistance was significantly lower 5, 10, 20, and 30 minutes after hemorrhage during BQ-123 infusion compared with hemorrhage alone at each time point. Infusion of BQ-123 into nonhemorrhaged rats had no effect on mean arterial pressure, systemic vascular resistance, or cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Zimmerman
R S
RS
Department of Endocrinology, Alton Ochsner Medical Foundation, New Orelans, LA.
Maymind
M
M
Barbee
R W
RW
D000818:Animals; D001794:Blood Pressure; D016232:Endothelins / Q000502:physiology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014655:Vascular Resistance
D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)