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Am J Physiol Regul Integr Comp Physiol (June 27, 2002). doi:10.1152/ajpregu.00620.2001
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Articles in PresS, published online ahead of print June 27, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00620.2001
Submitted on October 11, 2001
Accepted on June 13, 2002

Differential evolution of blood pressure and renal lesions after renin-angiotensin system blockade in Lyon hypertensive rats

Delphine Bertram1, Nelly Blanc-Brunat2, Jean Sassard1, and Ming Lo1*

1 Department of Physiology and Clinical Pharmacology, Faculty of Pharmacy, University of Lyon, Lyon, France
2 INSERM Unite, Hopital Edouard Herriot, Lyon, France

* To whom correspondence should be addressed. E-mail: mlo{at}rockefeller.univ-lyon1.fr.

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 nephro-protection which persist after its withdrawal. Male LH rats received orally from 3 to 12 weeks of age, either an angiotensin converting enzyme (ACE) inhibitor, perindopril, at the doses of 0.4 and 3 mg/kg/day, or an AT1 receptor antagonist, losartan, at the dose of 10 mg/kg/day. BP, histological changes in the kidney and urinary protein excretion were examined during and 10 weeks 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 the 3 mg/kg/day of perindopril while it remained slightly lower in those treated with 0.4 mg/kg/day of 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.




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