Ziai F, Ots M, Provoost A P, Troy J L, Rennke H G, Brenner B M, Mackenzie H S
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Kidney Int Suppl. 1996 Dec;57:S132-6.
The effects of chronic treatment with the specific AT1 angiotensin receptor antagonist, irbesartan, or the angiotensin converting enzyme inhibitor, enalapril, were assessed in uninephrectomized fawn-hooded hypertensive rats (FHH) and compared with vehicle treatment. Three days after uninephrectomy, irbesartan (240 mg/liter), enalapril (80 mg/liter) or vehicle were administered via the drinking water. Systolic blood pressure (SBP) and protein excretion rates (UprotV) were determined monthly. In rats receiving irbesartan (N = 7) and enalapril (N = 6) SBP (132 +/- 3 mm Hg and 133 +/- 6, respectively) was essentially normalized at 12 weeks when compared with vehicle (169 +/- 6 mm Hg (N = 6); all comparisons were P < 0.05 by ANOVA). Similarly, proteinuria was lower in irbesartan (44 +/- 12 mg/day) and enalapril (19 +/- 2) groups versus vehicle (123 +/- 10 mg/day). Treatment with both drugs was associated with marked reduction in glomerulosclerosis at 12 weeks (both < 5% vs. vehicle, 43 +/- 9%) without effect on glomerular volume. In identically prepared rats, glomerular capillary hydraulic pressure (PGC, estimated from stop-flow pressure, Psf) was lower in FHH receiving irbesartan (58 +/- 1 mm Hg, N = 6) or enalapril (54 +/- 2, N = 6) than in vehicle-treated rats, in whom PGC was greatly elevated (68 +/- 2 mm Hg; N = 7). Despite this, GFR and single nephron GFR were well maintained. These data support a critical role for AT1 receptor-mediated, angiotensin-dependent processes in the pathogenesis of hypertension in FHH, and further implicate elevated PGC as a major determinant of glomerular injury in this model.
在单侧肾切除的淡色带帽高血压大鼠（FHH）中评估了特异性AT1血管紧张素受体拮抗剂厄贝沙坦或血管紧张素转换酶抑制剂依那普利的长期治疗效果，并与溶剂治疗进行了比较。单侧肾切除三天后，通过饮用水给予厄贝沙坦（240毫克/升）、依那普利（80毫克/升）或溶剂。每月测定收缩压（SBP）和蛋白排泄率（UprotV）。在接受厄贝沙坦（N = 7）和依那普利（N = 6）的大鼠中，与溶剂组（169±6毫米汞柱，N = 6）相比，12周时SBP基本恢复正常（分别为132±3毫米汞柱和133±6毫米汞柱；通过方差分析，所有比较P < 0.05）。同样，厄贝沙坦组（44±12毫克/天）和依那普利组（19±2）的蛋白尿低于溶剂组（123±10毫克/天）。两种药物治疗均与12周时肾小球硬化的显著减轻相关（均<5%，而溶剂组为43±9%），对肾小球体积无影响。在同样制备的大鼠中，接受厄贝沙坦（58±1毫米汞柱，N = 6）或依那普利（54±2，N = 6）的FHH大鼠的肾小球毛细血管液压（PGC，根据停流压力Psf估算）低于溶剂治疗的大鼠，后者的PGC显著升高（68±2毫米汞柱；N = 7）。尽管如此，肾小球滤过率（GFR）和单个肾单位GFR仍保持良好。这些数据支持AT1受体介导的、血管紧张素依赖性过程在FHH高血压发病机制中的关键作用，并进一步表明升高的PGC是该模型中肾小球损伤的主要决定因素。
