title: ENDOTHELIN-1 SYTEM ACTIVITY IN ADULTS WITH BORDERLINE HIGH LDL-CHOLESTEROL.
abstract: BACKGROUND
  Modest elevations in plasma low-density lipoprotein (LDL)-cholesterol have been shown to confer a significant increase in cardiovascular risk. Endothelin (ET)-1 is a vasoconstrictor peptide with proatherogenic properties. The experimental aim of this study was to determine whether ET-1 system activity is elevated in adults with borderline high LDL-cholesterol, independent of other cardiometabolic abnormalities.
  
  
  METHODS
  Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of ET-1, selective ETAreceptor blockade (BQ-123), and non-selective ETA/Bblockade (BQ-123 + BQ-788) were determined in 40 middle-aged and older adults (45-70 years): 20 with optimal/near optimal LDL-cholesterol (<3.4 mmol/L) and 20 with borderline-high LDL-cholesterol (3.4-4.1 mmol/L).
  
  
  RESULTS
  Both groups demonstrated a similar, non-significant (~10%) reduction in FBF to ET-1. BQ-123 and BQ-123+788 elicited a modest, but significant, increase in FBF (~15-20%) in each group. However, there were no group differences in the FBF responses to either selective ETAor non-selective ETA/Breceptor antagonism.
  
  
  CONCLUSIONS
  Borderline-high LDL-C is not associated with increased ET-1 mediated vasoconstrictor tone. Disrupted ET-1 system activity may not contribute to the increased cardiovascular risk burden with borderline-high LDL-cholesterol.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Diehl
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 ; Integrative Vascular Biology Laboratory, Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045 ; Integrative Vascular Biology Laboratory, Denver Health Medical Center, Denver, CO 80204.
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.
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 ; Integrative Vascular Biology Laboratory, Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza