Sensitization of coronary α-adrenoceptor vasoconstriction in the prediabetic metabolic syndrome

Ü Deniz Dincer, Alberto G. Araiza, Jarrod D. Knudson, Patricia E. Molina, Johnathan Tune

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective: This study tested whether α-adrenoceptor-mediated coronary vasoconstriction is augmented in the metabolic syndrome and is accompanied by the alteration of specific α1-and α2-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 α1B-, α1D-, and α2A-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 α1-adrenoceptor agonist methoxamine (0.1-3 mg) or the α2-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 α1B-, α1D-, and α2A-adrenoceptor mRNA expression. However, Western blot analysis showed a significant decrease in α2A-adrenoceptor protein density with no change in α1B-or α1D-adrenoceptors. Methoxamine and BHT-933 produced dose-dependent decreases in coronary blood flow, but the decrease in coronary flow to methoxamine was significantly greater (∼ 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 α1- and α2-adrenoceptor signaling that could significantly limit control of coronary blood flow when the sympathetic nervous system is activated.

Original languageEnglish (US)
Pages (from-to)587-595
Number of pages9
JournalMicrocirculation
Volume13
Issue number7
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Vasoconstriction
Adrenergic Receptors
Methoxamine
Dogs
Fats
Real-Time Polymerase Chain Reaction
Messenger RNA
Sympathetic Nervous System
Arterioles
Epinephrine
Coronary Vessels
Norepinephrine
Proteins
Western Blotting

Keywords

  • α-adrenoceptor
  • Coronary blood flow
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Cardiology and Cardiovascular Medicine

Cite this

Sensitization of coronary α-adrenoceptor vasoconstriction in the prediabetic metabolic syndrome. / Deniz Dincer, Ü; Araiza, Alberto G.; Knudson, Jarrod D.; Molina, Patricia E.; Tune, Johnathan.

In: Microcirculation, Vol. 13, No. 7, 10.2006, p. 587-595.

Research output: Contribution to journalArticle

Deniz Dincer, Ü ; Araiza, Alberto G. ; Knudson, Jarrod D. ; Molina, Patricia E. ; Tune, Johnathan. / Sensitization of coronary α-adrenoceptor vasoconstriction in the prediabetic metabolic syndrome. In: Microcirculation. 2006 ; Vol. 13, No. 7. pp. 587-595.
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