title: 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.
abstract: OBJECTIVE
  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 blood pressure despite reduction of muscle sympathetic nerve activity. Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine. Unlike aliskiren and moxonidine, hydrochlorothiazide reduced urinary 8-iso-prostaglandin F2α-VI, a marker of oxidative stress. Vascular stiffness, systemic inflammation, leptin, adiponectin and other oxidative stress markers (plasma malondialdehyde, myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine) were unaffected by treatment.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johannes A N
authors.initials: JA
authors.lastname: Dorresteijn
authors.forename: Ilse M
authors.initials: IM
authors.lastname: Schrover
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
authors.forename: Peter G
authors.initials: PG
authors.lastname: Scheffer
authors.forename: P Liam
authors.initials: PL
authors.lastname: Oey
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
mesh_terms: D018592:Cross-Over Studies; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D010919:Placebos; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D004232:Diuretics; D010919:Placebos; D006852:Hydrochlorothiazide