title: Sensitization of coronary alpha-adrenoceptor vasoconstriction in the prediabetic metabolic syndrome.
abstract: OBJECTIVE
  This study tested whether alpha -adrenoceptor-mediated coronary vasoconstriction is augmented in the metabolic syndrome and is accompanied by the alteration of specific alpha(1)- and alpha(2)-coronary adrenoceptors.
  
  
  METHODS
  Studies were conducted in control and chronically high-fat-fed (6 weeks of 60% calories from fat) dogs with metabolic syndrome. Alterations in coronary alpha(1B)-, alpha(1D)-, and alpha(2A)-adrenoceptor mRNA and protein expression were examined by real-time PCR and Western analyses, respectively. Coronary blood flow and its response to intracoronary infusion of either the alpha1-adrenoceptor agonist methoxamine (0.1-3 mg) or the alpha(2)-adrenoceptor agonist BHT-933 (0.1-3 mg) were measured in anesthetized dogs.
  
  
  RESULTS
  Basal plasma epinephrine and norepinephrine levels were higher in the high-fat-fed dogs compared to controls. Real-time PCR revealed no alterations of coronary artery or arteriole alpha1B-, alpha(1D)-, and alpha(2A)-adrenoceptor mRNA expression. However, Western blot analysis showed a significant decrease in alpha(2A)-adrenoceptor protein density with no change in alpha(1B)- or alpha(1D)-adrenoceptors. Methoxamine and BHT-933 produced dose-dependent decreases in coronary blood flow, but the decrease in coronary flow to methoxamine was significantly greater (approximately 20%) in dogs with the metabolic syndrome. No differences in the coronary flow response to BHT-933 were noted.
  
  
  CONCLUSIONS
  These results indicate that the metabolic syndrome is associated with sensitization of alpha1- and alpha2-adrenoceptor signaling that could significantly limit control of coronary blood flow when the sympathetic nervous system is activated.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, USA.
authors.forename: U Deniz
authors.initials: UD
authors.lastname: Dincer
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Araiza
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Knudson
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001483:Base Sequence; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D004285:Dogs; D015870:Gene Expression; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology*; D008729:Methoxamine / Q000494:pharmacology; D011236:Prediabetic State / Q000235:genetics / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D017931:DNA Primers; D004041:Dietary Fats; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; C015603:azepexole; D008729:Methoxamine