Jackson B, Cubela R, Debrevi L, Whitty M, Johnston C I
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
J Cardiovasc Pharmacol. 1987;10 Suppl 10:S167-9.
Sprague-Dawley rats subjected to subtotal (1 7/8) nephrectomy or streptozotocin diabetes were treated with an angiotensin converting enzyme inhibitor or a calcium channel blocker and their course compared with untreated control animals. Subtotal nephrectomy led to hypertension, proteinuria, reduced creatinine clearance, and glomerulosclerosis over 6 weeks. Enalapril treatment (5 mg/kg/day, n = 11) or felodipine (30 mg/kg/day, n = 11) reduced systolic blood pressure to a comparable degree. Plasma creatinine (mumol/l) was lower after enalapril treatment (110 +/- 8, p less than 0.05) than with felodipine treatment (153 +/- 27) or no treatment (173 +/- 19, n = 18). Proteinuria (mg/24 h) was lower with enalapril treatment (15 +/- 3, p less than 0.001) than with no treatment (85 +/- 22) and increased with felodipine (221 +/- 35). Glomerulosclerosis was reduced with enalapril but not felodipine treatment. Diabetic rats were treated with enalapril (5 mg/kg/day, n = 17), verapamil (5 mg/kg/day, n = 17), or untreated. Diabetic rats had increased creatinine clearance (ml/min) compared with nondiabetic controls (1.52 +/- 0.06 vs. 1.15 +/- 0.05, n = 11, p less than 0.01). Enalapril and verapamil treatment reduced blood pressure equally. Enalapril but not verapamil reduced the elevated creatinine clearance of diabetic rats (enalapril, 1.37 +/- 0.04 ml/min, p less than 0.01; verapamil, 1.49 +/- 0.5 ml/min). Proteinuria (mg/24 h) was lower (p less than 0.05) with enalapril treatment (36 +/- 3) but not with verapamil treatment (58 +/- 10) in comparison to that in untreated diabetes (71 +/- 18).(ABSTRACT TRUNCATED AT 250 WORDS)
对接受次全(1又7/8)肾切除术或链脲佐菌素诱导糖尿病的Sprague-Dawley大鼠,给予血管紧张素转换酶抑制剂或钙通道阻滞剂治疗,并将其病程与未治疗的对照动物进行比较。次全肾切除术在6周内导致高血压、蛋白尿、肌酐清除率降低和肾小球硬化。依那普利治疗(5毫克/千克/天,n = 11)或非洛地平(30毫克/千克/天,n = 11)可使收缩压降低至相似程度。依那普利治疗后血浆肌酐(微摩尔/升)(110±8,p<0.05)低于非洛地平治疗组(153±27)或未治疗组(173±19,n = 18)。依那普利治疗组蛋白尿(毫克/24小时)(15±3,p<0.001)低于未治疗组(85±22),非洛地平治疗组蛋白尿增加(221±35)。依那普利治疗可减轻肾小球硬化,而非洛地平治疗则无此效果。糖尿病大鼠给予依那普利(5毫克/千克/天,n = 17)、维拉帕米(5毫克/千克/天,n = 17)或不治疗。与非糖尿病对照组相比,糖尿病大鼠肌酐清除率(毫升/分钟)增加(1.52±0.06对1.15±0.05,n = 11,p<0.01)。依那普利和维拉帕米治疗同等程度降低血压。依那普利可降低糖尿病大鼠升高的肌酐清除率(依那普利,1.37±0.04毫升/分钟,p<0.01;维拉帕米,1.49±0.5毫升/分钟),而维拉帕米则无此作用。与未治疗的糖尿病组相比,依那普利治疗组蛋白尿(毫克/24小时)降低(p<0.05)(36±3),而维拉帕米治疗组则未降低(58±10)(摘要截断于250字)