Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker
Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker
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DOI：
10.1093/ajh/hpu086
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Miura, Tetsuji
中科院分区：
文献类型：
--
作者：
Furuhashi, Masato;Moniwa, Norihito;Miura, Tetsuji
血管紧张素转换酶2（ACE 2）在肾脏中高度表达，并将血管紧张素（Ang）II转化为Ang-（1-7），一种肾脏保护肽。尿ACE 2已被证明是慢性肾脏疾病患者升高。然而，抗高血压药物对尿ACE2.METHODS的影响仍不清楚在2011年的Tanno-Sobetsu队列研究（n = 617）的参与者，不服药的受试者（n = 101）和用抗高血压药物治疗的高血压患者，包括钙通道阻滞剂氨氯地平和长效硝苯地平; ACE抑制剂依那普利;和血管紧张素Ⅱ受体阻断剂氯沙坦、坎地沙坦、缬沙坦、替米沙坦和奥美沙坦治疗1年以上（n = 100），并测定尿ACE 2水平。替米沙坦或奥美沙坦的剂量。依那普利治疗组的尿白蛋白与肌酐比值（UACR）显著高于对照组。奥美沙坦治疗组的尿ACE 2水平高于对照组，但其他治疗组的尿ACE 2水平均不高于对照组。尿ACE 2水平与收缩压（r = 0.211; P = 0.003）、尿肌酐清除率（r = 0.367; P < 0.001）和估计盐摄入量（r = 0.260; P < 0.001）呈正相关。多变量回归分析后调整的年龄，性别和相关指标显示，使用奥美沙坦是一个独立的预测尿ACE 2 level.CONCLUSIONSIn对比其他降压药物，奥美沙坦可能独特地增加尿ACE 2水平，这可能提供额外的肾脏保护作用。
BACKGROUNDAngiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney and converts angiotensin (Ang) II to Ang-(1-7), a renoprotective peptide. Urinary ACE2 has been shown to be elevated in patients with chronic kidney disease. However, the effects of antihypertensive agents on urinary ACE2 remain unclear.METHODSOf participants in the Tanno-Sobetsu cohort study in 2011 (n = 617), subjects on no medication (n = 101) and hypertensive patients treated with antihypertensive agents, including the calcium channel blockers amlodipine and long-acting nifedipine; the ACE inhibitor enalapril; and the Ang II receptor blockers losartan, candesartan, valsartan, telmisartan, and olmesartan, for more than 1 year (n = 100) were enrolled, and urinary ACE2 level was measured.RESULTSGlucose and hemoglobin A1c were significantly higher in patients treated with enalapril, telmisartan or olmesartan than in the control subjects. Urinary albumin-to-creatinine ratio (UACR) was significantly higher in patients treated with enalapril than in the control subjects. Urinary ACE2 level was higher in the olmesartan-treated group, but not the other treatment groups, than in the control group. Urinary ACE2 level was positively correlated with systolic blood pressure (r = 0.211; P = 0.003), UACR (r = 0.367; P < 0.001), and estimated salt intake (r = 0.260; P < 0.001). Multivariable regression analysis after adjustment of age, sex, and the correlated indices showed that the use of olmesartan was an independent predictor of urinary ACE2 level.CONCLUSIONSIn contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects.