[In contrast to captopril and enalapril, losartan does not increase mortality of gerbils after carotid ligation].
OBJECTIVE
To check wether the deleterious effect of enalaprilat administered before unilateral caroid ligation in the gerbil reported by Fernandez et al. (J Cardiovasc Pharmacol 1994; 24: 937) is not a molecule specific effect but an angiotensin converting enzyme inhibitor class effect.


METHODS
Survival rate of gerbils (an animal with incomplete Willis hexagona) was measured after unilateral carotid ligation with preadministration (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 was 65% in control, 62% in losartan, 30% in enalapril, 32% in enalapril + losartan, and 32% in captopril groups. Statistical analysis (log rank test) of the Kaplan-Meier survival curves over 72 hours showed no difference between losartan and controls nor between the various groups treated with ACEI. However survival was significantly lower in the ACEI groups than in the group treated by losartan alone (p < 0.02) or controls (p < 0.02). Intraaortic mean arterial pressure was measured in 6 controls, 6 animals treated with losartan and 6 other treated with enalapril. It was comparable in the losartan and enalapril treated animals (65 +/- 2 mm Hg vs 64 +/- 2) but significantly lower than in the controls (77 +/- 2 mmHg) (p < 0.02).


CONCLUSIONS
In contrast to oral preadministration of enalapril and captopril that of losartan does not increase the mortality of the gerbil after unilateral carotid ligation in spite of the same decrease in systemic blood pressure. Although a lower mortality than in controls was not observed with losartan as in the princeps study of Fernandez, these data are consistent with the demonstration by this author that angiotensin II plays a critical protective role in acute ischemia probably by promoting collateral circulation recruitment through non-AT1 receptors stimulation.
Mazouz
H
H
Service de néphrologie, Hôpital Sud, 80054 Amiens.
Oprisiu
R
R
Monge
M
M
Andrejak
M
M
Fournier
A
A
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000009:adverse effects* / Q000494:pharmacology; D013504:Cardiovascular Surgical Procedures / Q000401:mortality / Q000662:veterinary; D002339:Carotid Arteries / Q000601:surgery*; D004195:Disease Models, Animal; D004656:Enalapril / Q000009:adverse effects* / Q000494:pharmacology; D005849:Gerbillinae; D008026:Ligation; D019808:Losartan / Q000009:adverse effects* / Q000494:pharmacology; D017202:Myocardial Ischemia; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D016019:Survival Analysis
D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D004656:Enalapril; D002216:Captopril; D019808:Losartan