Decrease in rat cardiac beta1- and beta2-adrenoceptors by training and endurance exercise

Abstract

The cardiac β-adrenoceptor adaptation to physical activity was investigated in rats which were subjected to a six-week endurance swimming training (ET;n=7) and a training of high intensity (MT; n=7). In addition, the effect of a single bout of endurance exercise without preceding training (EE; n=7) was evaluated. These groups were compared with a sedentary control group (C; n=9). Beta-adrenergic receptors in rat myocardial membranes were labelled using the high affinity antagonist radioligand (−)¹²⁵iodocyanopindolol (ICYP). Computer modelling techniques provided estimates of the maximal binding capacity (B_max) and the dissociation constants (K_D). Tissue was constantly kept at temperatures of ≤4°C and incubated at 4°C for 18 h in buffer containing 100 μM GTP so as to prevent masking of β-adrenoceptors by endogenous norepinephrine. In comparison with the C group (B_max=43.2±1.6 fmol/mg protein, K_D=11.7±1.5 pM) computerized coanalyses of saturation binding data of ET, MT, and EE revealed a 13.0 %, 25.5 % and 16.6 % decrease in B_max (P<0.01), respectively, without significantly differing K_D values (10.6 pM, 9.0 pM, 10.5 pM, respectively). We provide the first evidence that acute exercise lowers the sarcolemmal β-adrenoceptor number in the rat heart. In the competition radioligand binding, CGP20712A and ICI118.551 were employed as subtype-selective antagonists of β₁- and β₂-adrenoceptors, respectively, to determine the relative proportions of the receptor subtypes. The ratio of $\text{β}{}_1\text{-}\text{β}{}_2\text{-}\text{adrenoceptors}$ in C was 67.5:32.5 and no statistically significant variation occured in animals subjected to physical activity. On the basis of published data we assume that acute exercise induces a sequestration of β-adrenoceptors from the cell surface to some intracellular compartment, whereas the molecular basis of the chronic β-adrenoceptor down-regulation may involve a training-induced reduction in receptor synthesis. Our findings on cardiac β-adrenoceptor adaptation to physical activity may represent one of the mechanisms underlying the relative bradycardia in trained subjects