title: Impaired fasting blood glucose is associated with increased endothelin-1 vasoconstrictor tone.
abstract: OBJECTIVE
  The experimental aim of this study was to determine whether ET-1-mediated vasoconstrictor tone is elevated in adult humans with impaired fasting blood glucose concentrations, independent of other cardiovascular risk factors.
  
  
  METHODS
  Forearm blood flow (FBF: plethysmography) responses to intra-arterial infusion of selective ETA receptor blockade (BQ-123: 100 nmol/min for 60 min) and non-selective ETA/B blockade (BQ-123 + BQ-788: 50 nmol/min for 60 min) were determined in 28 middle-aged, sedentary adults (17 M/11 F): 14 with normal fasting blood glucose (age: 57 ± 2 yr; 6 F/8 M; BMI: 29.2 ± 0.9 kg/m(2); glucose: 4.9 ± 0.1 mmol/L) and 14 impaired fasting blood glucose (58 ± 1 yr; 5 F/9 M; 29.6 ± 1.1 kg/m(2); 5.8 ± 0.1 mmol/L) concentrations.
  
  
  RESULTS
  Selective ETA receptor blockade elicited a significantly greater (∼20%) increase in FBF in the impaired fasting glucose adults compared with the normoglycemia controls. ETA/B blockade resulted in a further 2-fold increase (P < 0.05) in FBF above that elicited by ETA receptor antagonism in the impaired fasting glucose but not normal fasting glucose adults. There was a positive correlation between fasting blood glucose levels and the peak vascular responses to ETA (r = 0.44; P < 0.05) and ETA/B (r = 0.62; P < 0.05) blockade. No other anthropometric, hemodynamic or metabolic variable was correlated with the blood flow responses to ET-1 receptor blockade.
  
  
  CONCLUSIONS
  ET-1-mediated vasoconstrictor tone is elevated in adults with impaired fasting blood glucose concentrations, independent of other cardiometabolic risk factors. Enhanced ET-1 system activity may underlie endothelial vasomotor dysfunction and increased cardiovascular risk in adults with impaired fasting blood glucose concentrations.
authors: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors: Kyle J
authors: KJ
authors: Diehl
authors: Danielle L
authors: DL
authors: Templeton
authors: Julie
authors: J
authors: Ma
authors: Brian R
authors: BR
authors: Weil
authors: Jared J
authors: JJ
authors: Greiner
authors: Brian L
authors: BL
authors: Stauffer
authors: Christopher A
authors: CA
authors: DeSouza
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage; D010991:Plethysmography; D012307:Risk Factors; D057185:Sedentary Behavior; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
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