title: Elevated endothelin-1 vasoconstrictor tone in prehypertensive adults.
abstract: BACKGROUND
  Prehypertension (blood pressure [BP] 120-139/80-89 mm Hg) is an independent risk factor for hypertension and cardiovascular disease. Currently, it is unknown whether endothelin (ET)-1-mediated vasoconstrictor tone is elevated with BP in the prehypertensive range. The aims of this study were to determine whether ET-1 vasoconstrictor tone is elevated in prehypertensive adults and, if so, whether ET-1-mediated vasoconstriction contributes to endothelial vasodilator dysfunction in this population.
  
  
  METHODS
  Forearm blood flow responses to selective ET(A) receptor blockade (BQ-123; 100 nmol/min) were determined in 26 normotensive adults (age 55 ± 1 years; BP 112 ± 1/72 ± 1 mm Hg) and 30 prehypertensive adults (57 ± 1 years; BP 130 ± 1/80 ± 1 mm Hg). In a subset of participants, forearm blood flow responses to nonselective ET-1 receptor blockade (BQ-123 + BQ-788) were determined. Endothelium-dependent vasodilation to acetylcholine (8.0-32.0 μg/100 mL tissue/min) was measured in the absence and presence of selective ET(A) receptor blockade.
  
  
  RESULTS
  BQ-123 elicited a significantly greater increase in forearm blood flow in prehypertensive (approximately 20%) than in normotensive (approximately 5%) adults. Addition of BQ-788 resulted in a further increase (P < 0.05) in forearm blood flow in prehypertensive but not in normotensive adults. Forearm blood flow responses to acetylcholine were lower (P < 0.05) in prehypertensive (4.6 ± 0.3 to 12.6 ± 0.5 mL/100 mL tissue/min) than in normotensive (4.9 ± 0.3 to 14.7 ± 0.8 mL/100 mL tissue/min) adults. Co-infusion of BQ-123 did not affect acetylcholine-induced vasodilation in normotensive adults but resulted in an approximately 20% increase (P < 0.05) in prehypertensive adults.
  
  
  CONCLUSIONS
  ET-1-mediated vasoconstrictor tone is elevated with prehypertension, contributing to impaired endothelium-dependent vasodilation. ET-1 vasoconstriction may underlie the increased risk of hypertension and cardiovascular disease in prehypertensive adults.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.forename: Christian M
authors.initials: CM
authors.lastname: Westby
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001795:Blood Pressure Determination / Q000379:methods*; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D058246:Prehypertension / Q000503:physiopathology*; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D019332:Endothelin-1; D010456:Peptides, Cyclic; D009599:Nitroprusside; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)