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)