ß-Adrenoceptors in the transplanted human heart: unaltered ß-adrenoceptor density, but increased proportion of ß₂-adrenoceptors with increasing posttransplant time

Summary

To study whether in the (denervated) transplanted human heart ß-adrenoceptors are up-regulated we determined in right ventricular endomyocardial biopsies (weighing 2–7 mg) of 8 heart transplant recipients ß-adrenoceptor density and ß₁:ß₂-adrenoceptor ratio in weekly, later monthly intervals for 6 –18 posttransplant months. ß-Adrenoceptor density was assessed by 1–2 concentration (−)-[¹²⁵I]-iodocyanopindolol (ICYP, 200 and 150 pmol/l) binding, the ß₁:ß₂-adrenoceptor ratio by a ß₁-adrenoceptor saturating concentration of the selective ß₁-adrenoceptor antagonist CGP 20712 A (500 nmol/l). In biopsies taken from the donor hearts immediately before transplantation ß-adrenoceptor density was 64.5 ± 6.3 fmol ICYP bound/mg protein (n = 5), the ß₁ :ß₂-adrenoceptor ratio 81.2 ± 2.2:18.8 ± 2.2%. ß-ß-Adrenoceptor density did not change during the whole period investigated; it was in the first 9 posttransplant weeks 73.1±8.3 (n=22) and after 4–18 months 74.2 ± 7.6 fmol/mg protein (n = 16). In contrast, with increasing posttransplant time ß₁:ß₂-adrenoceptor ratio was shifted towards ß₂-adrenoceptors: in the first 9 weeks it was 80:20% (n = 17), after 16 weeks 75:25% (n = 10) and after 25–80 weeks 65:35% (n = 7). We conclude that in the first 18 posttransplant months ß-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decline in ß₁₋ and increase in ß₂-adrenoceptors: with increasing posttransplant time. As noradrenaline acts in the human heart solely at ß₁-adrenoceptors, while adrenaline activates both ß₁- and ß₂-adrenoceptors with about the same potency, with increasing posttransplant time (and increasing proportion of ß₂-adrenoceptors) adrenaline may play an important role for regulation of contractility and/or heart rate in heart transplant recipients.