Sensitization of Coronary α -Adrenoceptor Vasoconstriction in the Prediabetic Metabolic Syndrome

Authors: Deniz Dincer, Ü.; Araiza, Alberto; Knudson, Jarrod; Molina, Patricia; Tune, Johnathan

Source: Microcirculation, Volume 13, Number 7, October-November 2006 , pp. 587-595(9)

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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 α 1 - and α 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 α 1B -, α 1D -, and α 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 α 1 -adrenoceptor agonist methoxamine (0.1-3 mg) or the α 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 α 1B -, α 1D -, and α 2A -adrenoceptor mRNA expression. However, Western blot analysis showed a significant decrease in α 2A -adrenoceptor protein density with no change in α 1B - or α 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 (∼ 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 α 1 - and α 2 -adrenoceptor signaling that could significantly limit control of coronary blood flow when the sympathetic nervous system is activated.

Keywords: α-adrenoceptor; coronary blood flow; obesity

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10739680600885228

Affiliations: 1: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA

Publication date: 2006-10-01

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