Functional role of β2-adrenoceptors in the transplanted human heart

In the transplanted human heart, β-adrenoceptor subtypes change with time after transplantation: β 1 -adrenoceptors tend to decline, whereas β 2 -adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of β 2 -adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time: 932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the β 1 -adrenoceptor antagonist bisoprolol (10 mg p.o.; β 1 -adrenoceptor occupancy ∼80%; β 2 -adrenoceptor occupancy 35 ng/kg/min (p < 0.01). We conclude that in the transplanted human heart, β 2 -adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated β 2 -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.