Differential evolution of blood pressure and renal lesions after RAS blockade in Lyon hypertensive rats

Abstract

The present work aimed to assess, in Lyon hypertensive (LH) rats, whether an early and prolonged inhibition of the renin-angiotensin system (RAS) could result in a blood pressure (BP) lowering and nephroprotection that persist after its withdrawal. Male LH rats received orally from 3 to 12 wk of age either an angiotensin-converting enzyme inhibitor perindopril at the doses of 0.4 and 3 mg · kg−1· day−1or an AT1receptor antagonist losartan at the dose of 10 mg · kg−1· day−1. BP, histological changes in the kidney, and urinary protein excretion were examined during and 10 wk after cessation of the treatments. Both perindopril and losartan decreased BP, prevented renal lesions, and limited urinary protein excretion. After cessation of the treatment, BP returned to the level of never-treated LH rats in rats having received 3 mg · kg−1· day−1of perindopril while it remained slightly lower in those treated with 0.4 mg · kg−1· day−1of perindopril or with losartan. This lack of marked persistent antihypertensive effect contrasted with a durable decrease in urinary protein excretion and improvement of the renal histological lesions. In conclusion, it is possible to separate the BP-lowering effects of RAS blockade from those on glomerulosclerosis and urinary protein excretion.