Stornello M, Valvo E V, Scapellato L
Centro per lo Studio e la Terapia dell'Ipertensione, Ospedale Generale Umberto I, Siracusa, Italy.
Nephron. 1991;58(1):52-7. doi: 10.1159/000186378.
Arterial hypertension and proteinuric nephropathy are common features in diabetic patients. In streptozotocin-diabetic rats, it has been possible to reduce the blood pressure and proteinuria by converting enzyme inhibitors, and so slowing the decline of kidney function. These results have been confirmed in diabetic patients affected by arterial hypertension and persistent proteinuria. However, up to now it has not been clear if these favorable renal effects are related specifically to converting enzyme inhibition. In the attempt to clarify this last point, from a practical as well as from a speculative point of view, 12 type 2 diabetic outpatients affected by mild to moderate arterial hypertension and persistent macroalbuminuria (greater than 250 mg/daily, at least on three consecutive occasions) without any other signs of renal diseases were studied. In a randomized sequence and in a double blind fashion, after a washout period of 3 weeks, the patients underwent pharmacological treatment which consisted of enalapril 20 mg o.d., chlorthalidone 12.5 mg o.d., atenolol 50 mg o.d. and placebo o.d. Each treatment lasted 45 days. Kidney function, blood pressure and heart rate were checked at the beginning and at the end of each treatment, while urinary albumin excretion was measured at the end of the 4th, 5th, and 6th week of each treatment. Blood pressure significantly decreased in a similar fashion after each active treatment, while kidney function did not change significantly. Urinary albumin excretion rate significantly decreased after enalapril and atenolol, but did not change after chlorthalidone. According to these results we can hypothesize that the inhibition of tissue angiotensin formation and its related change on the glomerular permeability, rather than renal and systemic hemodynamic features, seem to be the common mechanisms by which both enalapril as well as atenolol decrease the albuminuria in our patients.
动脉高血压和蛋白尿性肾病是糖尿病患者的常见特征。在链脲佐菌素诱导的糖尿病大鼠中,使用转换酶抑制剂可以降低血压和蛋白尿,从而减缓肾功能的下降。这些结果在患有动脉高血压和持续性蛋白尿的糖尿病患者中得到了证实。然而,到目前为止,尚不清楚这些有益的肾脏效应是否与转换酶抑制作用有特定关联。为了从实际和推测的角度阐明这最后一点,我们研究了12名2型糖尿病门诊患者,他们患有轻度至中度动脉高血压和持续性大量蛋白尿(每日大于250毫克,至少连续三次),且无任何其他肾脏疾病迹象。在为期3周的洗脱期后,患者以随机顺序和双盲方式接受药物治疗,治疗药物包括依那普利每日20毫克、氯噻酮每日12.5毫克、阿替洛尔每日50毫克和安慰剂每日一次。每种治疗持续45天。在每种治疗开始和结束时检查肾功能、血压和心率,同时在每种治疗的第4、5和6周结束时测量尿白蛋白排泄量。每种活性治疗后血压均以相似方式显著下降,而肾功能无显著变化。依那普利和阿替洛尔治疗后尿白蛋白排泄率显著下降,但氯噻酮治疗后未改变。根据这些结果,我们可以推测,抑制组织血管紧张素的形成及其对肾小球通透性的相关改变,而非肾脏和全身血流动力学特征,似乎是依那普利和阿替洛尔降低我们患者蛋白尿的共同机制。