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Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats

Department of Pharma Research, Boehringer Ingelheim Pharma KG, Biberach, Germany, wienen{at}bc.boehringer-ingelheim.com

Serge Richard

Centre de Recherches Biologiques, 18800 Baugy, France

Pascal Champeroux

Centre de Recherches Biologiques, 18800 Baugy, France

Chantal Audeval-Gerard

Centre de Recherches Biologiques, 18800 Baugy, France

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day) and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus.

It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9—10 weeks. Animals were treated with telmisartan (3 or 10 mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n=18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/ day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.

Key Words: telmisartan • lisinopril • antihypertensive • hypertension • diabetes • renoprotection • angiotensin II receptor antagonist

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1, 31-36 (2001)
DOI: 10.3317/jraas.2001.005


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