Acta pharmacologica Sinica · 2008
Renoprotection persists after cessation of treatment with very low doses of perindopril in Lyon hypertensive rats.
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Egan Eleanor J, Dijoud Frédérique, Gilibert Sophie, Sassard Jean
Аннотация
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.
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.