In contrast to captopril or enalopril preadministration, that of losartan does not increase gerbil mortality after unilateral carotid ligation

Objective: To check wether the deleterious effect of enalaprilate administe red before unilateral carotid ligation in the gerbil reported by Fernandez et al. (J Cardiovasc Pharmacol 1994; 24: 937) is not a molecule specific ef fect but an angiotensin converting enzyme inhibitor class effect. Design and method: Survival rate of gerbils (an animal with incomplete Will is hexagona) was measured after unilateral carotid ligation with preadminis tration (2 hours before by gavage) of saline (0.75 ml) (n=37); losartan (20 mg/kg) (n=37), enalaparil (10 mg/kg) (n=37); a combination of losartan and enalapril at the same dose (n=37); and of captopril (75 mg/kg) (n=35). Results: The survival rate of the gerbils 72 hours after carotid ligation w as 65% in control. 62% in losartan, 30% in enalapril, 32% in enalapril + lo sartan, and 32% in captopril groups. Statistical analysis (log rank test) o f the Kaplan-Meier survival curves over 72 hours showed no difference betwe en losartan and controls nor between the various groups treated with ACEI. However survival was significantly lower in the ACEI groups than in the gro up treated by losartan alone (p<0.02) or controls (p<0.02). Intraaortic mea n arterial pressure was measured in 6 controls, 6 animals treated with losa rtan and 6 other treated with enalapril. It was comparable in the losartan and enalapril treated animals (65 +/-1:2 mm Hg vs 64 +/-2) but significantl y lower than in the controls (77 +/-2 mmHg) (p<0.02). Conclusions: In contrast to oral preadministration of enalapril and captopr il that of losartan does not increase the mortality of the gerbil after uni lateral carotid ligation in spite of the same decrease in systemic blood pr essure. Although a lower mortality than in controls was not observed with l osartan as in the princeps study of Fernandez, these data are consistent wi th the demonstration by this author that angiotensin II plays a critical pr otective role in acute ischemia probably by promoting collateral circulatio n recruitment through non-ATI receptors stimulation.