CARDIAC AUTONOMIC RECEPTORS - EFFECT OF LONG-TERM EXPERIMENTAL DIABETES

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Abstract
The effects of long-term streptozotocin-induced diabetes were studied on ventricular autonomic receptors. Left ventricle and lungs were removed from animals [rats] sacrificed either 3 or 6 mo. 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-mo. 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) were similar for all 3 classes of receptors in 3 mo. diabetic and control rats. The advancement of diabetes from 3 to 6 mo. produced a further decrease in .alpha. receptor number. Furthermore, ventricular .beta. and muscarinic receptors from 6 mo. diabetic rats demonstrated a large reduction in their densities as compared with their age-matched controls. As in the 3-mo. 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-mo. study demonstrated inhibitory constants (Ki) consistent with labeling .alpha.-1, .beta. and muscarinic receptors. Ki values were similar in control and diabetic tissues, with 1 exception: ventricular .alpha.-1 receptors were found to have a higher affinity for phenylephrine in the diabetic tissue. The binding characteristics of .alpha.-1, .beta. and muscarinic receptors were shown to be similar in the lung membranes obtained from either control or diabetic rats, both at either 3 and/or 6 mo. It appears that the effect of streptozotocin-induced diabetes is specific for the heart, as compared to the lung, and perhaps is not a generalized pattern in peripheral autonomic receptors. The receptor changes are probably due to the effects produced by hormonal derangements in the diabetic rats. [Implications with respect to altered drug responsiveness in human diabetics are presented].