Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker

Am J Hypertens. 2015 Jan;28(1):15-21. doi: 10.1093/ajh/hpu086. Epub 2014 May 18.


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.

Keywords: angiotensin II receptor blocker; angiotensin-converting enzyme 2; blood pressure; hypertension; olmesartan; urinary protein.; urine.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme 2
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / urine
  • Blood Pressure / drug effects
  • Case-Control Studies
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / enzymology
  • Hypertension / physiopathology
  • Hypertension / urine
  • Imidazoles / therapeutic use*
  • Japan
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptidyl-Dipeptidase A / urine*
  • Tetrazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation


  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Biomarkers
  • Imidazoles
  • Tetrazoles
  • olmesartan
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2