Characterization of Beta3-Adrenoceptors in Human Internal Mammary Artery and Putative Involvement in Coronary Artery Bypass Management

Abstract

ObjectivesThe aim of the present study was to analyze whether beta3-adrenoceptors (β3-ARs) were effectively present and functional in the human internal mammary artery (IMA).BackgroundThe beta1- and beta2-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 (β3).MethodsReverse 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.ResultsThe β3-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 β3-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by β1/β2-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human β3-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished the β3-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway.ConclusionsThose results demonstrated the presence of β3-ARs in the endothelial layer of human IMA. The present work highlights the role of β3-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension