Morin J P, Thomas N, Toutain H, Borghi H, Fillastre J P
INSERM U 295, UER Médecine, Saint-Etienne Du Rouvray.
Pathol Biol (Paris). 1989 Jun;37(5 Pt 2):652-6.
Perindopril, a new specific and potent inhibitor of angiotensin-I-converting enzyme was used to evaluate the possible participation of the inhibition of the renin-angiotensin system in the development of aminoglycoside-induced renal failure. Kidney function, morphology and biochemistry were evaluated at regular intervals throughout the study. Perindopril was given orally to rats at a daily dose of 2 mg/kg for 15 days prior to and during 15 day gentamicin treatment given intraperitoneally at a daily dose of 50 mg/kg. Perindopril treatment alone induced no modification in renal function or structure. Gentamicin treatment alone induced typical renal lesions which were scored as moderate and a slight but significant decrease in ACE blood levels. Concurrent treatment with perindopril and gentamicin induced a greater drop in ACE blood levels than after the administration of perindopril alone and produced more marked renal impairment than after the administration of gentamicin alone. These observations suggest that the integrity of the renin-angiotensin system may play an important role in limiting kidney injury during aminoglycoside induced nephrotoxicity.
培哚普利是一种新型的特异性强效血管紧张素转换酶抑制剂,用于评估抑制肾素-血管紧张素系统是否可能参与氨基糖苷类药物所致肾衰竭的发生过程。在整个研究过程中定期评估肾功能、形态学和生物化学指标。在腹腔注射每日剂量为50mg/kg庆大霉素治疗15天之前及治疗期间,给大鼠口服培哚普利,每日剂量为2mg/kg,持续15天。单独使用培哚普利对肾功能或结构无影响。单独使用庆大霉素可诱发典型的肾脏病变,病变程度为中度,同时ACE血液水平有轻微但显著的下降。培哚普利与庆大霉素联合治疗导致ACE血液水平下降幅度大于单独使用培哚普利,且导致的肾功能损害比单独使用庆大霉素更明显。这些观察结果表明,肾素-血管紧张素系统的完整性可能在限制氨基糖苷类药物所致肾毒性过程中的肾脏损伤方面发挥重要作用。