Heudes D, Michel O, Chevalier J, Scalbert E, Ezan E, Bariety J, Zimmerman A, Corman B
Institut National de la Santé et de la Recherche Médicale U 28, Broussais Hospital, Paris, France.
Am J Physiol. 1994 Mar;266(3 Pt 2):R1038-51. doi: 10.1152/ajpregu.1994.266.3.R1038.
The effect of angiotensin I-converting enzyme inhibition (ACEI) on the age-related changes in the kidney structure and function was investigated in rodents. Normotensive male Wistar (WAG)/Rij rats were treated with perindopril from the age of 6 mo to the day of killing at 12, 24, or 30 mo. Mean blood pressure, constant from 6 to 30 mo, was reduced by 19 mmHg in treated animals. With age, the major functional modifications were a decrease in glomerular filtration rate and in renal blood flow, a rise in intrarenal vascular resistance (IVR), a reduced tubular reabsorption of salts, and a progressive increase in proteinuria. ACEI significantly reduced IVR and proteinuria. From a structural point of view, the glomeruli showed 1) an increase in size, 2) a decrease in capillary surface, 3) a diffuse thickening of the glomerular basement membrane, 4) an expansion of the mesangial matrix, and 5) an accumulation of albumin droplets in podocytes inducing 6) a dispersed focal and segmental glomerulosclerosis which, at 30 mo, affected < 2% of glomeruli. Of these six age-related structural changes, ACEI delayed the appearance of the three latter changes.
在啮齿动物中研究了血管紧张素I转换酶抑制(ACEI)对肾脏结构和功能的年龄相关变化的影响。正常血压的雄性Wistar(WAG)/Rij大鼠从6月龄开始用培哚普利治疗,直至12、24或30月龄处死。治疗组动物的平均血压在6至30月龄保持稳定,但降低了19 mmHg。随着年龄增长,主要的功能改变包括肾小球滤过率和肾血流量降低、肾内血管阻力(IVR)升高、肾小管对盐的重吸收减少以及蛋白尿逐渐增加。ACEI显著降低了IVR和蛋白尿。从结构上看,肾小球表现出:1)大小增加;2)毛细血管表面积减少;3)肾小球基底膜弥漫性增厚;4)系膜基质扩张;5)足细胞中白蛋白滴积聚,导致6)散在的局灶节段性肾小球硬化,在30月龄时,<2%的肾小球受影响。在这六种与年龄相关的结构变化中,ACEI延缓了后三种变化的出现。