title: Elevations in C-reactive protein and endothelin-1 system activity in humans.
abstract: OBJECTIVE
  C-reactive protein (CRP) is an inflammatory cytokine that has been shown to be an independent predictor of future atherothrombotic events. Hyperactivity of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by the endothelium, is linked with cardiovascular disease development and progression. ET-1 is sensitive to inflammatory stimuli, though the influence of CRP on ET-1 system activity is unknown. We tested the hypothesis that ET-1-mediated vasoconstrictor tone is enhanced in adults with elevated plasma CRP concentrations.
  
  
  METHODS
  Sixty non-obese adults (43-70years) were studied: 20 with hsCRP<1.0mg/L (low CRP; 0.5±0.1mg/L); 20 with hsCRP 1.0-3.0mg/L (moderate CRP; 2.0±0.1mg/L); and 20 with hsCRP>3.0mg/L (high CRP; 6.3±0.5mg/L). Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial infusions of ET-1 (5pmol/min for 20min) and selective ETA receptor blockade (BQ-123, 100nmol/min for 60min).
  
  
  RESULTS
  In response to ET-1, FBF decreased ~10% in the low (-10.0±2.3%), moderate (-10.7±4.0%), and high (-6.6±5.2%) CRP groups, with no significant differences between groups. Additionally, all groups demonstrated a marginal, though significant (~10%), vasodilator response to BQ-123; however, there were no differences in the FBF response to BQ-123 across CRP groups. There were no significant correlations between plasma CRP concentrations and peak FBF response to either ET-1 or BQ-123.
  
  
  CONCLUSIONS
  These results indicate that ET-1 system activity is not influenced by elevations in CRP. Enhanced ET-1 system activity may not be involved in the increased cardiovascular disease risk associated with elevations in plasma CRP concentrations.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Dow
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Templeton
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Lincenberg
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045, USA; Denver Health Medical Center, Denver, CO 80204, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045, USA. Electronic address: desouzac@colorado.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010991:Plethysmography
chemical_list: D019332:Endothelin-1; D002097:C-Reactive Protein
keywords: C-reactive protein; Endothelin-1; Endothelium; Plethysmography