REDUCTION IN CANINE CARDIAC ??-ADRENERGIC RECEPTOR (??AR) DENSITY FOLLOWING CHRONIC ENDURANCE EXERCISE

Abstract

90 The goal of this project was to test the hypothesis that the increase in sympathetic tone associated with chronic, repetitive, endurance training results in a decreased density of βARs expressed in the myocardium. Mixed-breed dogs of either sex were either sedentary (cage-rested) or performed a nine week progressive treadmill exercise program (exercised). Half of the animals in each group received oral doses of the short-acting βAR antagonist, timolol, either daily (sedentary animals) prior to or during each bout of exercise. At the end of the training period, βAR density in myocardial microsomal membranes prepared from left ventricular wall tissue were determined using radioligand binding with 125I-cyanopindolol(125I-CYP). Specific 125I-CYP binding decreased (p<0.05) by≅40% (149 ± 34 fmol/mg protein) in myocardial membranes obtained from exercise animals compared to receptor density measured in membranes from untrained animals (250 ± 40 fmol/mg protein) with no apparent change in receptor affinity for the radioligand. βAR density measured in membranes from animals that received timolol treatment during exercise was not significantly different from sedentary controls. No significant change was observed in the ratio of β1 to β2-adrenergic receptors measured by competitive inhibition of 125I-CYP binding with the subtype-selective antagonists ICI-118,551 and atenolol. These data suggest that one adaptation that accompanies the remodeling of the myocardium during chronic exercise training is a downregulation of the βAR density.