title: Prehypertension is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation in sedentary adults.
abstract: BACKGROUND
  Endothelial vasodilator dysfunction contributes to the development of hypertension (blood pressure (BP) ≥ 140/90 mm Hg) and cardiovascular disease (CVD). Prehypertension (BP 120-139/80-89 mm Hg) has recently been identified as an independent risk factor for hypertension and CVD. It is currently unclear whether BP in the prehypertensive range is associated with endothelial vasodilator dysfunction. We tested the hypothesis that BP in the prehypertensive range, independent of other cardiovascular risk factors, is associated with impaired nitric oxide (NO)-mediated endothelium-dependent vasodilation.
  
  
  METHODS
  Forearm blood flow (FBF) responses to intra-arterial acetylcholine (ACh; 8.0-32.0 µg/100 ml tissue/min) and sodium nitroprusside (SNP; 1.0-4.0 µg/100 ml tissue/min) were measured in 20 normotensive (age: 56 ± 1 years; BP: 110/70 ± 1/2 mm Hg) and 20 prehypertensive (56 ± 2 years; 128/79 ± 2/2 mm Hg) adults. In addition, FBF responses to ACh were determined in the absence and presence of the endothelial NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (5 mg/min).
  
  
  RESULTS
  FBF responses to ACh were significantly lower (~30%) in prehypertensive (from 4.2 ± 0.3 to 11.4 ± 0.7 ml/100 ml tissue/min) compared with normotensive (from 4.6 ± 0.2 to 14.5 ± 0.7 ml/100 ml tissue/min) adults. There were no group differences in FBF responses to SNP. Co-infusion of L-NMMA significantly reduced the FBF response to ACh in the normotensive (~30%; P <0.05) but not the prehypertensive adults.
  
  
  CONCLUSIONS
  Prehypertension is associated with impaired NO-mediated endothelium-dependent vasodilation. The endothelial vasodilator dysfunction that characterizes hypertension is present at BP levels in the prehypertensive range and may contribute to the increased risk of hypertension and CVD in this population.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000109:Acetylcholine; D000328:Adult; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside; D058246:Prehypertension / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine