Inhibition of the renin-angiotensin system ameliorates genetically determined hyperinsulinemia

This study was performed in order to assess the potentially different effects of the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10 months: Control animals treated with placebo developed a metabolic syndrome with obesity (55.5 +/- 6.3 g), hypertension (146 +/- 10 mm Hg), hyperinsulinemia (7.2 +/- 5.7 ng/ml), hypercholesterolemia (5.1 +/- 0.7 mmol/l), cardiac hypertrophy (269 +/- 44 mg) and atherosclerotic plaques in the ascending aorta (3.6 +/- 1.5 mum(2)). Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist significantly (p < 0.001) reduces hypertension (73 +/- 5 and 78 +/- 11 mm Hg), cardiac hypertrophy (203 +/- 26 and 202 +/- 18 mg) and atherosclerosis (2.2 +/- 0.9 and 1.8 +/- 0.8 mum(2)). In addition, they prevented the development of obesity (42.2 +/- 3.5 and 38.3 +/- 2.8 g) and hyperinsulinemia (3.6 +/- 1.5 and 1.8 +/- 0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity and hyperinsulinemia in a genetically determined mouse model. (C) 2002 Elsevier Science B.V. All rights reserved.