Demeilliers B, Jover B, Mimran A
Renal and Hypertension Group, University Hospital Centre, Montpellier, France.
J Hypertens. 1995 Dec;13(12 Pt 2):1764-6.
Some observations have suggested that the harmful renal effects of angiotensin converting enzyme inhibitors might be partly mediated by non-angiotensin mechanisms under conditions in which a high intraglomerular pressure is required to maintain the glomerular filtration rate.
The effects of enalapril and losartan (10 and 30 mg/kg per 24 h for 6 days, respectively) on arterial pressure and renal function were assessed in one-kidney, one clip hypertensive rats subjected to dietary sodium depletion before treatment.
Arterial pressure and renal vascular resistance were reduced to a similar extent in rats treated with enalapril and with losartan. However, the glomerular filtration rate (867 +/- 40 mu l/min per g kidney weight in untreated rats) decreased to a greater extent in enalapril than in losartan-treated rats (284 +/- 29 and 444 +/- 32 mu l/min per g kidney weight, respectively). In addition, the filtration fraction was reduced in treated compared with untreated rats; however, it was slightly but significantly lower in enalapril- than in losartan-treated rats.
Despite similar final arterial pressure and renal vasodilation, angiotensin converting enzyme inhibitors may exert an effect on intrarenal forces contributing to the regulation of glomerular filtration rate, independently of blockade of the renin-angiotensin system.
一些观察结果表明,在需要高肾小球内压来维持肾小球滤过率的情况下,血管紧张素转换酶抑制剂对肾脏的有害作用可能部分由非血管紧张素机制介导。
在治疗前对单肾单夹高血压大鼠进行饮食性钠缺失处理,评估依那普利和氯沙坦(分别为每24小时10和30毫克/千克,持续6天)对动脉血压和肾功能的影响。
依那普利和氯沙坦治疗的大鼠动脉血压和肾血管阻力降低程度相似。然而,依那普利治疗的大鼠肾小球滤过率(未治疗大鼠为867±40微升/分钟每克肾重)下降幅度大于氯沙坦治疗的大鼠(分别为284±29和444±32微升/分钟每克肾重)。此外,与未治疗大鼠相比,治疗大鼠的滤过分数降低;然而,依那普利治疗的大鼠滤过分数略低于氯沙坦治疗的大鼠,且差异有统计学意义。
尽管最终动脉血压和肾血管舒张相似,但血管紧张素转换酶抑制剂可能对参与肾小球滤过率调节的肾内压力产生影响,这与肾素-血管紧张素系统的阻断无关。