Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management

OBJECTIVES The aim of the present study was to analyze whether beta(3)-adrenoceptors (beta(3)-ARs) were effectively present and functional in the human internal mammary artery (IMA). BACKGROUND The beta(1)- and beta(2)- adrenoceptors classically mediate the relaxant effects of catecholamines in the vessels. In vitro and in vivo studies performed in various animal species described vasodilating effects due to activation of a third beta-ARs subtype (beta(3)). METHODS Reverse transcription-polymerase chain reaction analysis, Western blot experiments, and pharmacological studies were carried out in human IMA samples harvested from 27 patients undergoing coronary bypass surgery. RESULTS The beta(3)-ARs messenger ribonucleic acid and protein were detected in intact IMA, but were absent in endothelium-free samples. This finding was confirmed by immunohistochemical experiments. In organ baths, a beta(3)-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by beta(1)/beta(2)-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human beta(3)-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished the beta(3)-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway. CONCLUSIONS Those results demonstrated the presence of beta(3)-ARs in the endothelial layer of human IMA. The present work highlights the role of beta(3)-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension. (c) 2005 by the American College of Cardiology Foundation.