Stevanovic Radomir D, Price Deborah A, Lansang M Cecilia, Fisher Naomi Dl, Laffel Lori Mb, Hollenberg Norman K
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
J Renin Angiotensin Aldosterone Syst. 2005 Sep;6(2):78-83. doi: 10.3317/jraas.2005.013.
Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2+/-1.5 years) and 37 normal subjects (37+/-2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6+/-1 ng/mL Ang I/hour in diabetic patients, and 1.7+/-0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1+/-17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2+/-13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.
糖尿病患者肾素 - 血管紧张素系统（RAS）的激活被认为与肾病的发生有关。血管紧张素转换酶抑制剂（ACE-I）和血管紧张素受体阻滞剂（ARB）对肾血管（RPF）反应的增强提示了这一点。评估RAS激活的另一种方法是在RAS阻断后评估肾素释放。44名连续入选的1型糖尿病患者（28.2±1.5岁）和37名高盐平衡的正常受试者（37±2.6岁）连续两天口服25毫克卡托普利和16毫克坎地沙坦。所有受试者均为白种人。除一名糖尿病患者外，所有患者肾功能均正常。在服用两种药物后4小时以及服用坎地沙坦后8小时和24小时测量血浆肾素活性（PRA）和肾血浆流量（RPF）。正如预期的那样，两种药物均增加了PRA。糖尿病患者卡托普利后的峰值反应（90分钟后）为5.6±1 ng/mL Ang I/小时，正常受试者为1.7±0.9 ng/mL Ang I/小时（p<0.001）。糖尿病患者中两种药物的反应在PRA（r = 0.623；p = 0.001）和RPF（r = 0.9；p<0.001）方面具有相关性。当卡托普利的PRA反应低于中位数时，RPF反应受限（22.1±17.6 ml/分钟/1.73 m²）。当高于中位数时，RPF反应也更大（62.2±13.9 ml/分钟/1.73 m²；p = 0.006）。肾素对ACE-I和ARB的反应证实了糖尿病患者RAS的激活。
