Dworkin L D, Levin R I, Benstein J A, Parker M, Ullian M E, Kim Y, Feiner H D
Department of Medicine, New York University Medical Center, New York 10016.
Am J Physiol. 1990 Oct;259(4 Pt 2):F598-604. doi: 10.1152/ajprenal.1990.259.4.F598.
Male Munich-Wistar rats underwent right nephrectomy and were given weekly injections of deoxycorticosterone acetate (DOCA) and 1% saline (salt) to drink. Two studies were performed. In the first, rats given enalapril (ENP) were compared with controls. In the second, rats ingested either standard chow or chow to which the calcium-entry blocker nifedipine (NIF) had been added. Six to eight weeks after nephrectomy, both control DOCA-salt rats and those given ENP had severe hypertension and significant proteinuria. Rats given NIF excreted less protein, and glomerular lesions were not observed in this group. The effects of NIF on several parameters that have been associated with glomerular injury were examined. Micropuncture studies revealed that glomerular capillary pressure was increased in DOCA-salt rats and was not reduced by NIF. Platelet aggregation was also similar in NIF-treated and control rats. Morphometric studies revealed a tendency toward lower glomerular volume of NIF-treated rats; however, kidney weight and glomerular capillary radius were unaffected by therapy. Thus NIF, but not ENP, prevents DOCA-salt rats from developing hypertension and glomerular injury. This effect does not depend on reduction in glomerular pressure or inhibition of platelet aggregation.
雄性慕尼黑-维斯特大鼠接受了右肾切除术,并每周注射醋酸脱氧皮质酮(DOCA),同时饮用1%的盐水。进行了两项研究。在第一项研究中,将给予依那普利(ENP)的大鼠与对照组进行比较。在第二项研究中,大鼠分别摄入标准饲料或添加了钙通道阻滞剂硝苯地平(NIF)的饲料。肾切除术后6至8周,对照DOCA-盐大鼠和给予ENP的大鼠均出现严重高血压和明显蛋白尿。给予NIF的大鼠蛋白质排泄减少,且该组未观察到肾小球病变。研究了NIF对与肾小球损伤相关的几个参数的影响。微穿刺研究表明,DOCA-盐大鼠的肾小球毛细血管压力升高,且NIF未使其降低。NIF治疗组和对照组大鼠的血小板聚集情况也相似。形态计量学研究显示,NIF治疗组大鼠的肾小球体积有降低趋势;然而,肾脏重量和肾小球毛细血管半径不受治疗影响。因此,NIF而非ENP可防止DOCA-盐大鼠发生高血压和肾小球损伤。这种作用并不依赖于肾小球压力的降低或血小板聚集的抑制。