Beta-adrenoceptor subtypes in human coronary artery: desensitization of beta 2-adrenergic vasorelaxation by chronic beta 1-adrenergic stimulation in vitro.
We previously demonstrated that right atrial strips from patients treated with beta 1-selective antagonists exhibit sensitization of beta 2-adrenergic responses in vitro. We also showed that cardiac beta 2-adrenergic sensitization can be induced in normal subjects prospectively by beta 1-blocker treatment. To determine whether such cross-talk could be induced in vitro, we studied beta-adrenoceptor-mediated vasorelaxation in deendothelialized rings of human coronary artery from patients undergoing cardiac transplantation. After incubation with 10 microM phenoxybenzamine for 1 h, concentration-effect curves were determined to norepinephrine (NE) and epinephrine (EPI), with or without 300 nM CGP 20712A (a beta 1-selective antagonist), 50 nM ICI 118551 (a beta 2-selective antagonist), or both antagonists. Both beta 1- and beta 2-adrenergic components to vasorelaxation were detected. Other rings were incubated for 16 h with either 1 microM NE (a selective beta 1-adrenoceptor agonist) or 300 nM CGP 20712A, or both. After washout, concentration-effect curves were determined to EPI in the presence of 300 nM CGP 20712A (beta 2-adrenergic responses). No differences in beta 2-adrenergic vasorelaxation were noted after prolonged incubation with either CGP 20712A or the combination of CGP 20712A and NE.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferro
A
A
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, England.
Kaumann
A J
AJ
Brown
M J
MJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D016027:Heart Transplantation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; C049763:CGP 20712A; D009638:Norepinephrine; D004837:Epinephrine