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

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

Research output: Contribution to journalArticle

24 Scopus citations

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 1 2006

Keywords

  • Coronary blood flow
  • Obesity
  • α-adrenoceptor

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Deniz Dincer, Ü., Araiza, A. G., Knudson, J. D., Molina, P. E., & Tune, J. D. (2006). Sensitization of coronary α-adrenoceptor vasoconstriction in the prediabetic metabolic syndrome. Microcirculation, 13(7), 587-595. https://doi.org/10.1080/10739680600885228