Tajiri Y, Umeda F, Inoguchi T, Kunisaki M, Nawata H, Ninomiya H, Asano T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Diabetes Res. 1990 Mar;13(3):145-50.
Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.
最近，一些研究者报道了卡托普利（一种血管紧张素转换酶抑制剂）对糖尿病肾病，尤其是蛋白尿的有益作用。然而，蛋白尿减少的机制尚未阐明。本研究旨在评估卡托普利对非胰岛素依赖型糖尿病（NIDDM）患者尿白蛋白排泄的影响，并探讨其与尿前列腺素（PGs）排泄的关系。13例糖尿病患者口服卡托普利（37.5毫克/天），疗程为8周。同时对这些患者进行一次卡托普利（12.5毫克）的单次给药。清晨及单次给药后2小时收集即时尿样。8例患者（A组）在4周内白蛋白指数（毫克/克肌酐）显著下降，但5例患者（B组）未发现下降。此外，在A组中，单次服用卡托普利后，6-酮-前列腺素F1α（前列环素I2的稳定代谢产物）和前列腺素E2的尿排泄量显著增加（p<0.05），而血栓素B2（血栓素A2的稳定代谢产物）的尿排泄量无显著变化。糖尿病患者中显著较低（p<0.05）的尿6-酮-前列腺素F1α/血栓素B2比值在A组中显著升高（p<0.01）至正常水平。然而，在B组中，尿PGs排泄无显著变化。这些结果表明，卡托普利可增强肾内血管舒张性PGs如前列环素I2和前列腺素E2的生成，这可能与降低糖尿病患者肾小球内毛细血管压力和尿蛋白排泄密切相关。
