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

Bertrand Rozec, MD^_*,, Sabrina Serpillon, PhD^_*, Gilles Toumaniantz, PhD^_*, Camille Sèze, MSc^_*, Yohann Rautureau, PhD, Olivier Baron, MD, Jacques Noireaud, PhD^_* and Chantal Gauthier, PhD^_*,||,_*

^_* L’Institut du Thorax, INSERM UMR533, Faculté de Médecine, Nantes, France
Département d’anesthésie et de réanimation chirurgicale, CHRU G et R Laënnec, Nantes, France
Department of Veterinary Basic Science, Royal Veterinary College, London, United Kingdom
Service de chirurgie thoracique et cardiovasculaire, CHRU G et R Laënnec, Nantes, France
^|| Faculté des Sciences et Techniques, Université de Nantes, Nantes, France

Manuscript received December 16, 2004; revised manuscript received March 22, 2005, accepted March 29, 2005.

^_* Reprint requests and correspondence: Dr. Chantal Gauthier, L’Institut du Thorax, UMR533, Faculté de Médecine, 1 rue Gaston Veil, BP 53508, F-44035 Nantes, France (Email: chantal.gauthier{at}nantes.inserm.fr).

OBJECTIVES: The aim of the present study was to analyze whether beta₃-adrenoceptors (ß₃-ARs) were effectively present and functional in the human internal mammary artery (IMA).

BACKGROUND: The 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 (ß₃).

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 ß₃-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 ß₃-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by ß₁/ß₂-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human ß₃-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished the ß₃-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway.

CONCLUSIONS: Those results demonstrated the presence of ß₃-ARs in the endothelial layer of human IMA. The present work highlights the role of ß₃-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension.

Abbreviations and Acronyms   Ach = acetylcholine   CABG = coronary artery bypass graft   IMA = internal mammary artery   LIPE = hormone-sensitive lipase   L-NMMA = NG-monomethyl-L-arginine monoacetate   NO = nitric oxide   PE = phenylephrine   RT-PCR = reverse transcription-polymerase chain reaction   -AR = alpha-adrenoceptor   ß-AR = beta-adrenoceptor