Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension

Abstract

Background Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20mg of olmesartan (N = 40) or 5mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24. Results Both olmesartan and amlodipine treatment for 24weeks decreased systolic and diastolic blood pressures significantly by > 18mmHg and > 8mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5pg/mL → 46.2 ± 59.4pg/mL) than by amlodipine treatment (29.2 ± 38.9pg/mL → 31.7 ± 26.0pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42ng/mL → 6.74 ± 0.39ng/mL by olmesartan treatment vs. 6.43 ± 0.23ng/mL → 6.61 ± 0.42ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r = − 0.252 and r = − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria. Conclusions These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015.