Acta Pharmacologica Sinica 2008 November; 29 (11): 1296-1300; doi: 10.1111/j.1745-7254.2008.00862.x

Aim: The possibility that angiotensin-converting enzyme inhibitors can protect hypertensive kidneys independently of any blood pressure (BP) decrease remains a matter of controversy. The present study investigates this theory in Lyon genetically-hypertensive (LH) rats.

Methods: Male rats were used in the present study and were untreated (controls) or orally received 0.4, 0.1, 0.04, and 0.01 mg·kg^-1·d^-1 doses of perindopril from 3 to 17 weeks of age. At 16 and 23 weeks of age (ie during treatment and 6 weeks after its cessation), systolic BP (SBP) was measured by plethysmography, and urine was collected to measure the urinary protein (Uprot) and N-acetyl-seryl-aspartyl-lysyl-proline-to-creatinine (Cr) concentrations. The kidneys were dissected for a semiquantitative histological analysis.

Results: SBP was significantly lowered (-18%±2% and -11%±1% from controls at 16 and 23 weeks, respectively) with a 0.4 mg·kg^-1·d^-1 dose of perindopril. Lower doses did not affect SBP. Uprot/Cr decreased, and Ac-SDKP/Cr increased with all the doses of perindopril used. Uprot/Cr remained lower at 23 weeks in the rats treated with 0.1 mg·kg^-1·d^-1 and smaller doses. The ratio of Uprot/Cr was closely (r=0.6) related to the histological lesions score.

Conclusion: In LH rats, low doses of perindopril induce renoprotection which is independent of SBP decrease and persists after withdrawal of treatment.

Keywords: rat; hypertension; kidney; angiotensin-converting enzyme inhibitor; proteinuria