Petitjean P, Vloemans M, Barthelmebs M, Stephan D, Grima M, Jund A, Imbs J L
Institut de pharmacologie, URA D0589 CNRS, Université Louis Pasteur, Strasbourg, France.
Fundam Clin Pharmacol. 1994;8(4):356-65. doi: 10.1111/j.1472-8206.1994.tb00813.x.
The effects on renal function of quinapril, an angiotensin I converting enzyme (ACE) inhibitor, and of nifedipine, a dihydropyridine calcium antagonist, were studied in the early stages of diabetes in rats. Wistar rats received one injection of streptozotocin (STZ) to induce diabetes; the hyperglycaemia was then controlled with daily insulin therapy (2-3 units NPH insulin/rat). One week after STZ injection, rats were treated orally with quinapril (0.3 or 3 mg/kg/d) or nifedipine (30 mg/kg/day) for 1 week, after which renal functions were compared with those of untreated diabetic rats or non-diabetic control rats. At the end of these two weeks, diabetic rats had gained less weight and had developed renal hypertrophy and glomerular hyperfiltration (3.21 +/- 0.23 vs 2.36 +/- 0.09 ml/min for non-diabetic rats, mean +/- SEM, P < 0.01). Their urinary albumin excretion was higher, as was the urinary excretion of water, sodium, potassium, urea and glucose. One week treatment with quinapril or nifedipine had no significant effect on the increase in the glomerular filtration rate (respectively 2.97 +/- 0.18 and 2.99 +2- 0.15 ml/min). Quinapril and nifedipine differed with regard to their effects on urinary albumin excretion. Albuminuria was increased by nifedipine but not by quinapril (respectively 0.554 +/- 0.158 and 0.149 +/- 0.046 mg/day/100 g BW, P < 0.05). This difference between the effects of the dihydropyridine and the ACE inhibitor on albuminuria may be linked to different effects on the glomerular functions.
在大鼠糖尿病早期阶段,研究了血管紧张素I转换酶(ACE)抑制剂喹那普利和二氢吡啶类钙拮抗剂硝苯地平对肾功能的影响。Wistar大鼠接受一次链脲佐菌素(STZ)注射以诱导糖尿病;然后通过每日胰岛素治疗(2 - 3单位中性鱼精蛋白锌胰岛素/大鼠)控制高血糖。STZ注射一周后,大鼠口服喹那普利(0.3或3毫克/千克/天)或硝苯地平(30毫克/千克/天),持续1周,之后将肾功能与未治疗的糖尿病大鼠或非糖尿病对照大鼠进行比较。在这两周结束时,糖尿病大鼠体重增加较少,出现了肾肥大和肾小球高滤过(非糖尿病大鼠为2.36 +/- 0.09毫升/分钟,糖尿病大鼠为3.21 +/- 0.23毫升/分钟,平均值 +/- 标准误,P < 0.01)。它们的尿白蛋白排泄量更高,水、钠、钾、尿素和葡萄糖的尿排泄量也更高。用喹那普利或硝苯地平治疗一周对肾小球滤过率的增加没有显著影响(分别为2.97 +/- 0.18和2.99 +/- 0.15毫升/分钟)。喹那普利和硝苯地平对尿白蛋白排泄的影响有所不同。硝苯地平增加了蛋白尿,但喹那普利没有(分别为0.554 +/- 0.158和0.149 +/- 0.046毫克/天/100克体重,P < 0.05)。二氢吡啶类药物和ACE抑制剂对蛋白尿影响的这种差异可能与对肾小球功能的不同影响有关。