Effect of angiotensin II receptor blockade by [Sar1-Ala8]angiotensin II in hemorrhagic shock.
An angiotensin II receptor antagonist, [Sar1-Ala8]angiotensin II (saralasin), was infused at 60 (microgram/kg)/h into cats to examine its effect in hemorrhagic shock. Aprotinin (1,000 (KIU/kg)/h) was also 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 additional cats receiving either saralasin or its vehicle. Hemorrhaged cats treated with saralasin revealed a postoligemic preservation of mean arterial bloood pressure and superior mesenteric artery blood flow (SMAF). Final pressures were 48 +/- 12 mmHg and 81 +/- 9 mmHg with vehicle and saralasin treatment, respectively, and final SMAF were 2.5 +/- 0.5 (ml/kg)/min in cats receiving vehicle and 5.5 +/- 0.6 (ml/kg)/min in those receiving saralasin. Total plasma proteolysis was diminished by both saralasin and aprotinin, exhibiting elevations of free amino-nitrogen groups of 2.5-fold and 2-fold over initial as compared to a 3.5-fold elevation in vehicle-treated shocked cats. Myocardial depressant factor (MDF) activities were also suppressed by saralasin compared to shocked cats receiving vehicle (24 +/- 4 units vs. 59 +/- 3 units). These results indicate that blockade of angiotensin II actions in hemorrhagic shock is beneficial.
D000596:Amino Acids / Q000097:blood; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000502:physiology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002403:Cathepsins / Q000097:blood; D002415:Cats; D004359:Drug Therapy, Combination; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D012504:Saralasin / Q000494:pharmacology*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology*
D000596:Amino Acids; D009201:Myocardial Depressant Factor; D000804:Angiotensin II; D007611:Aprotinin; D002403:Cathepsins; D010447:Peptide Hydrolases; D012504:Saralasin