Functional Role of β2-Adrenoceptors in the Transplanted Human Heart

In the transplanted human heart, β-adrenoceptor subtypes change with time after transplantationβ1-adrenoceptors tend to decline, whereas β2-adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of β2-adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the β1-adrenoceptor antagonist bisoprolol (10 mg p.o.; β1-adrenoceptor occupancy ∼80%; β2-adrenoceptor occupancy 35 ng/kg/min (p < 0.01). We conclude that in the transplanted human heart, β2-adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated β2-adrenoceptors or by the fact that during isoprenaline infusion, vagal activity increases, thus blunting the response in the native (innervated) but not in the transplanted (denervated) sinus node.