Increased β-adrenergic receptor density in an experimental model of cardiac transplantation

We examined β-adrenergic receptor density, basal, maximal isoproterenol and fluoride-stimulated adenylate cyclase activities, and morphologic characteristics of rabbit and rat native and heterotopic isograft cardiac tissue. Four weeks after graft placement there were only subtle histologic differences between native and graft tissue. Membrane preparations from isografts of rabbits demonstrated increases in β-receptor density (maximum [³H]DHA binding = 111 ± 19.3 fmol/mg versus 52.4 ± 4.9 in native hearts, p < 0.05). In a small number of experiments, rat isografts also demonstrated a suggestive increase in β-receptor density (69.8 ± 7.1 fmol/mg versus 40.2 ± 7.3 in native hearts). Isoproterenol-stimulated adenylate cyclase activity was greater in rabbit graft hearts (3.98 ± 0.20 x basal activity) than in native tissue 2.67 ± 0.16 x basal activity, p < 0.05). We conclude that cardiac denervation may lead to a postsynaptic form of β-adrenergic supersensitivity that is due to an increase in β-receptor density.