Coexistence of at least three distinct beta-adrenoceptors in human internal mammary artery.
The internal mammary artery (IMA) is currently the preferred conduit for myocardial revascularization. However, perioperative vasospasm and a hypoperfusion state during maximal exercise may limit its use as a bypass graft. The mechanism of spasm has not been clearly defined. Since beta-adrenoceptor activation plays a major role in vasorelaxation, the present study was carried out to investigate the beta-adrenoceptor responsiveness of human IMA smooth muscle. Isoproterenol produced a concentration-dependent relaxation in endothelium-denuded IMA segments, precontracted with phenylephrine (maximal relaxation 46.33+/-5.45%). Atenolol (10(-6)M) and propranolol (2x10(-7)M) inhibited isoproterenol-induced relaxation. While atenolol produced partial inhibition, propranolol caused a complete inhibition in a majority of the segments and a partial inhibition in a minority. BRL 37344, a selective beta 3-adrenoceptor agonist, produced a concentration-dependent relaxation in phenylephrine-precontracted rings of endothelium-denuded IMA (maximal relaxation 40.35+/-4.07%). Cyanopindolol, a beta-adrenoceptor partial agonist, produced a marked relaxation (58.65+/-6.2%) in endothelium-denuded IMA rings, precontracted with phenylephrine. Cyanopindolol-induced relaxation was resistant to blockade by propranolol (2x10(-7)M). Spontaneous contractions of IMA rings were also observed in some cases that were inhibited by isoproterenol and BRL 37344. This observation implies the important role of beta-adrenoceptor activation in prevention of human IMA spasm. The results obtained in present study indicate that human IMA smooth muscle possesses an atypical beta-adrenoceptor together with beta1- and beta2-adrenoceptors. Regarding the relaxation induced in IMA rings by adding BRL 37344, the possible identical entities of IMA atypical beta-adrenoceptors and beta 3-adrenoceptors are suggested.
Shafiei
M
M
Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran.
Omrani
G
G
Mahmoudian
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents