Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker.
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.
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; furuhasi@sapmed.ac.jp.
Masato
M
Furuhashi
Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan;
Norihito
N
Moniwa
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Tomohiro
T
Mita
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Takahiro
T
Fuseya
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Shutaro
S
Ishimura
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Kohei
K
Ohno
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Satoru
S
Shibata
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Marenao
M
Tanaka
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Yuki
Y
Watanabe
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Educational Development, Sapporo Medical University Center for Medical Education, Sapporo, Japan;
Hiroshi
H
Akasaka
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan;
Hirofumi
H
Ohnishi
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Hideaki
H
Yoshida
Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan;
Hideki
H
Takizawa
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Nursing, Division of Medical and Behavioral Subjects, Sapporo Medical University School of Health Sciences, Sapporo, Japan;
Shigeyuki
S
Saitoh
Sapporo Nishimaruyama Hospital, Sapporo, Japan;
Nobuyuki
N
Ura
Sapporo Medical University, Sapporo, Japan.
Kazuaki
K
Shimamoto
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
Tetsuji
T
Miura
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000085962:Angiotensin-Converting Enzyme 2; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology / Q000652:urine; D007093:Imidazoles / Q000627:therapeutic use*; D007564:Japan; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000652:urine*; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
angiotensin II receptor blocker; angiotensin-converting enzyme 2; blood pressure; hypertension; olmesartan; urinary protein.; urine