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 language | English |
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Pages (from-to) | 587-595 |
Number of pages | 9 |
Journal | Microcirculation |
Volume | 13 |
Issue number | 7 |
DOIs | |
State | Published - Oct 2006 |
Keywords
- Coronary blood flow
- Obesity
- α-adrenoceptor