title: Coronary vasomotor reactivity to endothelin-1 in the prediabetic metabolic syndrome.
abstract: OBJECTIVE
  The purpose of the present investigation was to test the hypothesis that coronary vasoconstrictor responses to endothelin-1 are augmented in the prediabetic metabolic syndrome.
  
  
  METHODS
  ELISA was used to measure plasma endothelin-1 and intracoronary endothelin-1 dose-response experiments were conducted in vivo on normal control and high-fat-fed prediabetic dogs. Additionally, isolated left circumflex (LCX) coronary arteries and arterioles (< 160 microm) were used for in vitro functional studies and molecular analyses (quantitative real-time PCR and Western blotting).
  
  
  RESULTS
  Plasma endothelin-1 concentrations were not different between control and prediabetic dogs. Coronary vasoconstriction to endothelin-1 was similar in control and prediabetic dogs, both in vivo and in isolated arterioles. Nonetheless, real-time PCR analysis revealed significant decreases in ET(A) receptor transcript levels in LCX coronary arteries and arterioles. Also, Western blotting revealed a significant decrease in ET(A) receptor protein in LCX coronary arteries.
  
  
  CONCLUSIONS
  The findings of the present investigation indicate that although ET(A) receptor-signaling is sensitized by induction of the metabolic syndrome, endothelin-mediated coronary vasoconstriction does not significantly contribute to coronary dysfunction at this early stage of prediabetes.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Knudson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rogers
authors.forename: U Deniz
authors.initials: UD
authors.lastname: Dincer
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Araiza
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dick
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D024821:Metabolic Syndrome / Q000503:physiopathology*; D011236:Prediabetic State / Q000503:physiopathology; D044022:Receptor, Endothelin A / Q000032:analysis / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A