Bryer-Ash M, Fraze E B, Luetscher J A
Department of Medicine, Stanford University School of Medicine, California 94305.
J Clin Endocrinol Metab. 1988 Feb;66(2):454-8. doi: 10.1210/jcem-66-2-454.
PRA, active renin, and prorenin were measured in 32 normotensive diabetic patients and 14 normal subjects of similar ages before and after iv injection of 40 mg furosemide. The majority of the diabetic patients had normal PRA and active renin levels before and after furosemide, but in 4 normal subjects and 5 diabetic patients PRA did not rise after furosemide treatment to at least 0.25 ng angiotensin I/(L.s) as previously found in 90% of normal subjects. Two thirds of the diabetic patients had higher plasma prorenin levels than the normal subjects. Four of the 5 diabetic patients whose PRA failed to rise to the usual level after furosemide treatment attained a plasma prorenin level higher than any normal subject, suggesting that furosemide stimulated synthesis and secretion of prorenin, but that conversion of prorenin to active renin was impaired. These 5 diabetic patients also had higher plasma creatinine and potassium levels as well as an increased frequency of albuminuria compared with the other diabetic patients. In contrast, the 4 normal subjects whose PRA failed to reach the usual level after furosemide treatment had low unresponsive prorenin levels, indicating that furosemide did not evoke the expected increase in prorenin or renin synthesis. We conclude that the inability of some diabetic patients to increase PRA after furosemide treatment is not dependent on failure of renin synthesis, but reflects an impairment of the normal processing of prorenin, leading to high levels of prorenin in plasma.
在32例血压正常的糖尿病患者和14例年龄相仿的正常受试者静脉注射40mg速尿前后,分别测量了他们的血浆肾素活性(PRA)、活性肾素和肾素原。大多数糖尿病患者在速尿注射前后的PRA和活性肾素水平正常,但有4例正常受试者和5例糖尿病患者在速尿治疗后PRA未升至至少0.25ng血管紧张素I/(L·s),而此前在90%的正常受试者中可观察到这一水平升高。三分之二的糖尿病患者血浆肾素原水平高于正常受试者。在速尿治疗后PRA未能升至正常水平的5例糖尿病患者中,有4例的血浆肾素原水平高于任何正常受试者,这表明速尿刺激了肾素原的合成和分泌,但肾素原向活性肾素的转化受损。与其他糖尿病患者相比,这5例糖尿病患者的血浆肌酐和钾水平也更高,蛋白尿的发生率也更高。相比之下,在速尿治疗后PRA未能达到正常水平的4例正常受试者的无反应性肾素原水平较低,这表明速尿并未引起预期的肾素原或肾素合成增加。我们得出结论,一些糖尿病患者在速尿治疗后无法增加PRA并非取决于肾素合成失败,而是反映了肾素原正常加工过程的受损,导致血浆中肾素原水平升高。