title: Vascular effects of nebivolol added to hydrochlorothiazide in African Americans with hypertension and echocardiographic evidence of diastolic dysfunction: the NASAA study.
abstract: BACKGROUND
  African Americans have greater risk of cardiovascular events than comparator populations of white European origin. A potential reason for this is reduced nitric oxide bioavailability in African Americans, resulting in increased prevalence of factors that contribute to ventricular dysfunction. We investigated the effects of nebivolol with the diuretic hydrochlorothiazide (HCTZ) in hypertensive African Americans with echocardiographic evidence of diastolic dysfunction.
  
  
  METHODS
  A total of 42 African American patients were assigned to nebivolol and HCTZ in an open-label fashion for a 24-week period. Changes in blood pressure (BP), echocardiographic parameters, and success in attaining target BP were determined. As an indirect determinant of endothelial function, serum total nitric oxide (NOx) levels and asymmetric dimethyl arginine (ADMA) levels were performed at baseline and after the treatment period.
  
  
  RESULTS
  The systolic BP decreased from 150 ± 13 to 136 ± 16 mm Hg (P < .005). Diastolic BP decreased from 94 ± 13 to 84 ± 9 mm Hg (P = .008). Of the patients that completed the study, 77% achieved a combined target BP of systolic BP <140 mm Hg and a diastolic BP <90 mm Hg. Serum NOx increased by 41% and 39% in patients that were treated with 10 mg and 20 mg daily nebivolol, respectively. The ADMA levels decreased by 44% following treatment. The change in systolic BP was strongly correlated to the change in ADMA (r = .54; P = .024). Furthermore, in comparison to a group of age-matched patients controlled with diuretic therapy only, the ADMA levels were significantly lower in the nebivolol posttreatment group (controlled BP with diuretic: 0.32 ± 0.07μmol/L; nebivolol posttreatment: 0.24 ± 0.06 μmol/L; P < .05).
  
  
  CONCLUSIONS
  Reduced BP with nebivolol in hypertensive African Americans and echocardiographic evidence of diastolic dysfunction correlates with improved endothelial function. Furthermore, improvement in endothelial function and increased nitric oxide bioavailability suggests a potential mechanism of efficacy of nebivolol in these patients.
authors.affiliation: Atlanta Vascular Research Foundation, Atlanta, GA 30084, USA. bobby.khan@atlantaclinicalresearch.com
authors.forename: Bobby V
authors.initials: BV
authors.lastname: Khan
authors.forename: Syed T
authors.initials: ST
authors.lastname: Rahman
authors.forename: Tahir
authors.initials: T
authors.lastname: Haque
authors.forename: Nadya
authors.initials: N
authors.lastname: Merchant
authors.forename: Sujan
authors.initials: S
authors.lastname: Bhaheetharan
authors.forename: Junior
authors.initials: J
authors.lastname: Harris
authors.forename: Kanwal
authors.initials: K
authors.lastname: Umar
authors.forename: Jessica
authors.initials: J
authors.lastname: Wahi
authors.forename: Keith C
authors.initials: KC
authors.lastname: Ferdinand
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001578:Benzopyrans / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004452:Echocardiography; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D054144:Heart Failure, Diastolic / Q000473:pathology*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D009566:Nitrates; D009573:Nitrites; D000068577:Nebivolol; D006852:Hydrochlorothiazide; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine