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

作　　者：Eleanor J EGAN Frédérique DIJOUD Sophie GILIBERT Jean SASSARD 

机构地区：[1]Département de Physiologie et Pharmacologic Clinique Faculté de Pharmacie-Lyon [2]Laboratoire d'anatomo-pathologie-Hópital Debrousse-Lyon, France

出　　处：《Acta Pharmacologica Sinica》2008年第11期1296-1300,共5页中国药理学报（英文版）

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 ofperindopril 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 ofperindopril. 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.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 ofperindopril 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 ofperindopril. 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.

关 键 词：rat HYPERTENSION KIDNEY angiotensin-converting enzyme inhibitor PROTEINURIA 

分 类 号：R544.1[医药卫生—心血管疾病]