Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker

作者：Furuhashi Masato^*; Moniwa Norihito; Mita Tomohiro; Fuseya Takahiro; Ishimura Shutaro; Ohno Kohei; Shibata Satoru; Tanaka Marenao; Watanabe Yuki; Akasaka Hiroshi; Ohnishi Hirofumi; Yoshida Hideaki; Takizawa Hideki; Saitoh Shigeyuki; Ura Nobuyuki; Shimamoto Kazuaki; Miura Tetsuji

来源：American Journal of Hypertension, 2015, 28(1): 15-21.

DOI：10.1093/ajh/hpu086

• angiotensin-converting enzyme 2
• angiotensin II receptor blocker
• blood pressure
• hypertension
• olmesartan, urine, urinary protein

BACKGROUND
Angiotensin-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.
METHODS
Of 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.
RESULTS
Glucose 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.
CONCLUSIONS
In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects.

• 出版日期2015-1