Premium
Sensitization of Coronary α ‐Adrenoceptor Vasoconstriction in the Prediabetic Metabolic Syndrome
Author(s) -
DINCER Ü. DENIZ,
ARAIZA ALBERTO G.,
KNUDSON JARROD D.,
MOLINA PATRICIA E.,
TUNE JOHNATHAN D.
Publication year - 2006
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680600885228
Subject(s) - methoxamine , medicine , endocrinology , vasoconstriction , alpha (finance) , adrenergic receptor , sensitization , epinephrine , agonist , receptor , immunology , construct validity , nursing , patient satisfaction
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.