Characteristics of myocardial beta-adrenergic receptors during endotoxicosis in the rat

The effects of in vivo endotoxin administration on beta-adrenergic receptors in rat ventricle membranes were studied using [3H]dihydroalprenolol as a radioligand. Nonlinear regression analysis of saturation binding indicated one-site binding of antagonist in both control and endotoxic tissues. There was no change in maximum binding or dissociation constant of [3H]dihydroalprenolol at 0.5 or 3 h after endotoxin administration or when the rats were in the agonal stage of shock. Isoproterenol competition studies revealed that there was an increase in the slope of the curve from endotoxic tissues at the agonal stages (0.6 +/- 0.06 vs. 0.91 +/- 0.12, control and endotoxic, respectively, P less than 0.05) and that there was a decrease in affinity for isoproterenol binding. Control binding modeled to a two-state fit, whereas binding to endotoxin-exposed membranes modeled to one state of lower affinity. These data suggest that there is an alteration in receptor-adenylate cyclase coupling, which may account for an attenuation of agonist-stimulated cyclase activity. A modification in the beta-adrenergic receptor may contribute to the decrease in myocardial performance during shock.