Rumble J R, Doyle A E, Cooper M E
Department of Medicine, University of Melbourne, Heidelberg Repatriation/Austin Hospitals, Australia.
Am J Hypertens. 1995 Jan;8(1):53-7. doi: 10.1016/0895-7061(94)00165-8.
The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.
本研究的目的是在遗传性高血压合并糖尿病的模型中，比较血管紧张素转换酶（ACE）抑制剂与钙通道阻滞剂对肾脏的影响。将链脲佐菌素诱导的糖尿病模型建立在自发性高血压大鼠（SHR）身上。然后将动物随机分为不治疗组、ACE抑制剂培哚普利组或二氢吡啶类钙拮抗剂拉西地平组。在为期32周的研究期间，连续评估体重、收缩压、血糖控制、肾功能和白蛋白排泄率（AER）。在第32周时处死动物并测量肾小球体积。两种降压方案均显著降低了糖尿病SHR的收缩压。在第32周时，三组之间的血糖控制、血清肌酐或肾小球滤过率没有显著差异。ACE抑制剂培哚普利在32周内显著降低了AER和肾小球肥大，而钙拮抗剂拉西地平未能降低AER或肾小球肥大。因此，与ACE抑制的效果相反，拉西地平的钙通道阻滞尽管显著降低了血压，但在该模型中未能减轻肾脏损伤。这些结果支持了这样一种假设，即尽管对全身血压有相似的影响，但不同的降压方案对糖尿病肾脏的保护能力可能不同。
