Renoprotection persists after cessation of treatment with very low doses of perindopril in Lyon hypertensive rats
Abstract
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:
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.