Cardiac autonomic receptors: effect of long-term experimental diabetes

Abstract

The present study was undertaken to study the effects of long-term streptozotocin-induced diabetes on ventricular autonomic receptors. Left ventricle and lungs were removed from animals sacrificed either 3 or 6 months after streptozotocin administration (65 mg/kg). Diabetic rats were significantly smaller and had elevated serum glucose and reduced serum insulin values as compared with their age-matched controls. The alpha-1, beta adrenergic and muscarinic cholinergic receptors were identified and characterized utilizing [3H]prazosin, [3H]dihydroalprenolol and [3H]quinuclidinyl benzilate, respectively. Saturation studies showed that in the 3-month study, ventricular alpha-1 receptor density was significantly decreased in diabetic rats while beta and muscarinic receptor numbers exhibited only a slight reduction in their number. Equilibrium, dissociation constants or (KD), however, were similar for all three classes of receptors in 3 month diabetic and control rats. The advancement of diabetes from 3 to 6 months produced a further decrease in alpha receptor number. Furthermore, ventricular beta and muscarinic receptors from 6 month diabetic rats demonstrated a large reduction in their densities as compared with their age-matched controls. As in the 3-month study, the KD values were not affected by the induction of diabetes in any of the receptor systems studied. Inhibition (competition) studies performed in ventricular membranes from the 6-month study demonstrated inhibitory constants (Ki) consistent with labeling alpha-1, beta and muscarinic receptors. Ki values were similar in control and diabetic tissues with one exception: ventricular alpha-1 receptors were found to have a higher affinity for phenylephrine in the diabetic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)