Hypophagic effect of the angiotensin AT1 receptor antagonist irbesartan in rats

Recent experimental and clinical studies report beneficial metabolic effects of antiltypertensive drugs interfering with angiotensin. Antagonists at the angiotensin AT(1) receptor can reduce blood glucose and triglyceride levels. So far, there is little evidence, however, that angiotensin AT(1) receptor antagonists can also affect food intake. Particularly unknown is if drugs of this class can have acute effects on short term feeding. To address this issue, the angiotensin AT(1) receptor antagonist irbesartan was studied in a one-hour feeding paradigm in rats. In this study, irbesartan was investigated in comparison with fenfluramine, an established satiating drug, and the angiotensin converting enzyme (ACE) inhibitor. captopril. We found a significant reduction of one-hour food intake following 100-200 mg/kg (i.p.) irbesartan. The ACE inhibitor captopril (25- 100 mg/kg i.p.) remained without effect on food intake and fenfluramine showed the expected hypophagic action starting at 1 mg/kg (i.p.). The hypophagic effect of irbesartan could not be attributed to sedation or any gross effect on motor activity as determined both upon feeding and independent activity experiments. Fenfluramine (1 mg/kg) and irbesartan (100 mg/kg) did not reduce the latency to feed, but similarly reduced the eating rate at the beginning of the test meal. In conclusion, the present study demonstrates a hypophagic effect of the angiotensin AT(1) receptor antagonist irbesartan that cannot be attributed to sedation or antidipsic effects of the drug. (c) 2007 Elsevier B.V. All rights reserved.