Effect of angiotensin II receptor blockade by [Sar1-Ala8]angiotensin II in hemorrhagic shock

Abstract

An angiotensin II receptor antagonist, [Sar1-Ala8]angiotensin II (saralasin), was infused at 60 (.mu.g/kg) per h into cats to examine its effect in hemorrhagic shock. Aprotinin (1000 (kIU/kg) per h) was administered to cats to determine how kinin inhibition effects angiotensin receptor blockade in shock. Saralasin was infused into shocked and sham-shocked cats. Aprotinin was administered to cats receiving saralasin or its vehicle. Hemorrhaged cats treated with saralasin revealed a postoligemic preservation of mean arterial blood pressure and superior mesenteric artery blood flow (SMAF). Final pressures were 48 .+-. 12 mm Hg and 81 .+-. 9 mm Hg with vehicle and saralasin treatment, respectively, and final SMAF were 2.5 .+-. 0.5 (ml/kg) per min in cats receiving vehicle and 5.5 .+-. 0.6 (ml/kg) per min in those receiving saralasin. Total plasma proteolysis was diminished by saralasin and aprotinin, exhibiting elevations of free amino-N groups of 2.5 and 2-fold over initial as compared to a 3.5-fold elevation in vehicle-treated shocked cats. Myocardial depressant factor (MDF) activities were suppressed by saralasin compared to shocked cats receiving vehicle (24 .+-. 4 units vs. 59 .+-. 3 units). Blockade of angiotensin II actions in hemorrhagic shock seems beneficial.