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

• 来源期刊: 中国药理学报（英文版）
• 关键词: rat hypertension kidney angiotensin-converting enzyme inhibitor proteinutia
• 年，卷（期）: 2008,（11）
• 页码范围: 1296-1300
• 页数: 5页
• 语种: 英文
• DOI: 10.1111/j.1745-7254.2008.00862.x

摘要

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 histologi-cal analysis. Results: S BP 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 Up-rot/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.