Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management.
OBJECTIVE
The aim of the present study was to analyze whether beta3-adrenoceptors (beta3-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 (beta3).


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 beta3-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 beta3-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by beta1/beta2-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human beta3-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished the beta3-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway.


CONCLUSIONS
Those results demonstrated the presence of beta3-ARs in the endothelial layer of human IMA. The present work highlights the role of beta3-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension.
Rozec
Bertrand
B
L'Institut du Thorax, INSERM UMR533, Faculté de Médecine, Nantes, France.
Serpillon
Sabrina
S
Toumaniantz
Gilles
G
Sèze
Camille
C
Rautureau
Yohann
Y
Baron
Olivier
O
Noireaud
Jacques
J
Gauthier
Chantal
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D008323:Mammary Arteries / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes; C076252:amibegron