ANGIOTENSIN-II RECEPTOR BLOCKADE LIMITS GLOMERULAR INJURY IN RATS WITH REDUCED RENAL MASS
ANGIOTENSIN-II RECEPTOR BLOCKADE LIMITS GLOMERULAR INJURY IN RATS WITH REDUCED RENAL MASS
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DOI：
10.1172/jci115949
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发表时间：
1992-09-01
影响因子：
15.9
通讯作者：
MEYER, TW
中科院分区：
文献类型：
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作者：
LAFAYETTE, RA;MAYER, G;MEYER, TW
在肾单位数目减少的大鼠中，比较了血管紧张素II（AII）阻断剂与血管紧张素转换酶抑制剂的作用。将大鼠进行六分之五肾消融，并在2周后分为4组，血压和血清肌酐值相似。然后，第1组作为未处理的对照组，而第2组接受AII受体拮抗剂MK 954（先前已被指定为DuP 753），第3组接受转化酶抑制剂依那普利，第4组接受利血平、肼屈嗪和氢氯噻嗪的组合。10周后进行显微穿刺和形态学研究。转换酶抑制、AII受体阻断和联合治疗方案在逆转全身性高血压方面同样有效（时间平均收缩压：第1组，185+/-5 mmHg;第2组，125+/-2 mmHg;第3组，127+/-2 mmHg;第4组，117+/-4 mmHg）。微穿刺研究显示，通过抑制转化酶和阻断AII可显著降低肾小球跨毛细血管压，但联合治疗方案不能显著降低肾小球跨毛细血管压（Δ P：第1组，49+/-1 mmHg;第2组，42+/-1 mmHg;第3组，40+/-2 mmHg;第4组，47+/-1 mmHg）。在接受依那普利和MK 954的大鼠中，全身血压降低与蛋白尿和节段性肾小球硬化的发生显著减少相关，但在接受联合方案的大鼠中则不然（肾小球硬化病变的患病率：第1组，41+/-4%;第2组，9+/-1%;第3组，9+/-1%;第4组，33 +/-6%）。这些结果表明，转换酶抑制剂对残余肾小球功能和结构的影响取决于AII活性的降低，不能简单地归因于全身血压的正常化。
The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185+/-5 mmHg; group 2, 125+/-2 mmHg; group 3, 127+/-2 mmHg, group 4, 117+/-4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta-P: group 1, 49+/-1 mmHg; group 2, 42+/-1 mmHg; group 3, 40+/-2 mmHg, group 4, 47+/-1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41+/-4%; group 2, 9+/-1 %; group 3, 9+/-1 %; group 4,33+/-6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure.