Differential effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trial

Objectives: The objective of this study is to determine the effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension. Methods: A randomized, four-way, double-blind, crossover study in 31 adults with previously untreated obesity-related hypertension, in which the effects of 8 weeks' inhibition of the renin-angiotensin-aldosterone system (using aliskiren 300 mg), sympathoinhibition (using moxonidine 0.4 mg), diuretic therapy (using hydrochlorothiazide 25 mg) or placebo on flow-mediated dilation and 24-h blood pressure were compared. Results: The median flow-mediated dilation during placebo was 4.0% [interquartile range (IQR) 2.9-5.5%] and was increased by aliskiren [0.81%, 95% confidence interval (CI) 0.02-1.79], but not by moxonidine (0.20%, 95% CI -0.46 to 1.03) or hydrochlorothiazide (0.39%, 95% CI -0.31%-1.26%). Similarly, compared with placebo, mean 24-h blood pressure was most reduced by aliskiren (-9.8/-6.3 mmHg) and to a lesser degree by hydrochlorothiazide (-5.9/-2.6 mmHg). Moxonidine did not significantly affect b Conclusion: Renin inhibition, but not sympathoinhibition or diuretic therapy, improves endothelial function and results in larger reductions of 24-h, office, and central blood pressure in obesity-related hypertension. This adds weight to the hypothesis that inhibition of the renin-angiotensin-aldosterone system is an effective first step in the treatment of obesity-related hypertension.