Regional Distribution of β-Adrenoceptors in the Human Heart

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Abstract
We evaluated the amount of .beta.1- and .beta.2-adrenoceptors in human right and left atrium as well as in right and left ventricular wall obtained from heart transplant recipients who suffered from end-stage congestive cardiomyopathy. The total number of myocardial .beta.-adrenoceptors was assessed with the nonsubtype selective .beta.-adrenoceptor radioligand (-)[125I]iodocyanopindolol (ICYP); concomitantly, the number of .beta.1-adrenoceptors was determined with the selective .beta.1-adrenoceptor radioligand (-)[3H]bisoprolol. The number of .beta.2-adrenoceptors was calculated by subtracting (-)[3H]bisoprolol binding sites from ICYP binding sites. With this technique, a .beta.1/.beta.2-ratio of .apprx. 65/35% for both atria and of .apprx. 75/25% for both ventricles was found. Identical results were obtained when the .beta.1/.beta.2-ratio was calculated indirectly by nonlinear regression analysis of competition curves of the selective .beta.1-adrenoceptor antagonist bisoprolol and the selective .beta.2-adrenoceptor antagonist ICI 118,551 with ICYP binding. In addition, on atria and on ventricles, adenylate cyclase was activated by norepinephrine (presumably by .beta.1- and .beta.2-adrenoceptor stimulation) and by procaterol (by .beta.2-adrenoceptor stimulation). It is concluded that in the human heart functional .beta.1- and .beta.2-adrenoceptors coexist on both atria and both ventricles. In end-stage congestive cardiomyopathy, there appears to be a selective down-regulation of cardiac .beta.1-adrenoceptors, whereas .beta.2-adrenoceptors are obviously not affected. This may explain the beneficial effects of .beta.2-adrenoceptor agonists in severe heart failure.