β-Adrenoceptor Subtypes in Human Coronary Artery

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Abstract
We β1-eviously demonstrated that right atrial strips from patients treated with β1 -selective antagonists exhibit sensitization of β2-adrenergic responses in vitro. We also showed that cardiac β2-adrenergic sensitization can be induced in normal subjects β1-ospectively by β1-blocker treatment. To determine whether such cross-talk could be induced in vitro, we studied β-adrenoceptor-mediated vasorelaxation in deendothelialized rings of human coronary artery from patients undergoing cardiac transplantation. After incubation with 10 μM phenoxy-benzamine for 1 h, concentration-effect curves were determined to norepinephrine (NE) and epinephrine (EPI), with or without 300 nM CGP 20712A (a β1-selective antagonist), 50 nM ICI 118551 (a β2-selective antagonist), or both antagonists. Both β1- and β2-adrenergic components to vasorelaxation were detected. Other rings were incubated for 16 h with either 1 μM NE (a selective β1-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 (β2-adrenergic responses). No differences in β2-adrener-gic vasorelaxation were noted after prolonged incubation with either CGP 20712A or the combination of CGP 20712A and NE. However, after incubation with 1 μM NE, β2-adrenergic vasorelaxation was desensitized, with a threefold reduction in potency (p < 0.05) and a 45% decrease in efficacy (p < 0.05); this occurred with no change in β1-adrenergic vasorelaxation, as assessed by concentration-effect curves to NE in the presence of 50 nM ICI 118551. These results provide the first evidence that cross-talk between β1- and β2-adrenoceptors can be induced in vitro. The cross-desensitization observed may be the inverse effect of the previously observed β2-adre-nergic sensitization in response to chronic β1-blockade.

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