Effects of Experimental Diabetes on Adrenergic and Cholinergic Receptors of Rat Myocardium

  1. Rebecca Kennedy
  1. Departments of Medicine and Physiology, Duke University Medical Center Durham, North Carolina Montefiore Hospital, Albert Einstein College of Medicine Bronx, New York
  1. Address reprint requests to R. Sanders Williams, MD., Box 3945, Duke University Medical Center, Durham, North Carolina 27710.

Abstract

To more fully characterize the alterations in myocardial adrenergic and cholinergic receptors induced by the diabetic state, we investigated the binding characteristics of (–) [3H] dihydroalprenolol to beta adrenergic receptors (bAR), [3H] prazosin to alpha adrenergic receptors (aAR), and [3H] quinuclidinyl-benzilate to muscarinic cholinergic receptors (MCR) in myocardial membranes derived from rats 8 wk after treatment with streptozotocin. We also studied an equal number of animals from three control groups: free-eating nondi-abetics, pair-weighted nondiabetics, and streptozoto-cin-treated animals treated daily with insulin.

Diabetic hearts demonstrated 27% fewer bAR (P < 0.01) and 31% fewer aAR (P < 0.01) than free-eating controls, without changes in MCR, and without changes in antagonist affinity, agonist affinity, or agonist slope factor (pseudo-Hill coefficient) for any class of receptors. Food restriction had no effect on receptor characteristics, and treatment of diabetic rats with insulin prevented any downregulation of cardiac bAR or aAR.

The parallel decrease in both bAR and aAR suggests that streptozotocin-induced hypothyroidism is not the primary causative factor of bAR downregulation in this model, since hypothyroidism produces upregulation of aAR. Furthermore, the lack of change in cardiac MCR suggests that the adrenergic receptor alterations are not the result of nonspecific abnormalities of protein synthesis in the diabetic heart. Further studies are required to establish the physiologic significance of these receptor alterations, but these data support the hypothesis that altered adrenergic receptor properties may underlie, at least in part, the chronotropic and inotropic abnormalities of cardiac performance that are associated with the diabetic state.

  • Received December 31, 1982.
| Table of Contents