Adrenal catecholamine metabolism and myocardial adrenergic receptors in streptozotocin diabetic rats.

Adrenal medullary function and myocardial adrenergic receptors were investigated in streptozotocin-treated diabetic rats. The animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and killed 60 days after treatment. Adrenal tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) activities were increased by 52, 28 and 39%, respectively, in the STZ diabetic rats. In addition, adrenal concentrations of dopamine (+52%) norepinephrine (+46%), and epinephrine (+33%) were elevated significantly (P less than 0.05). Increased adrenal TH activity reflected an increased Vmax, but no change in Km. Receptor densities (Bmax), determined by [3H]prazosin and [3H]dihydroalprenolol binding, were decreased by 24 and 25%, respectively, in the myocardium of 60-day diabetic rats. Insulin-induced chronic hypoglycemia in the STZ diabetic rats produced a marked increase in the adrenal TH concentration (Vmax, +65% or +225%, respectively), as compared to control or diabetic rats, without changes in the affinity (Km) for the substrate. These results suggest that the STZ diabetic rat has abnormalities of catecholaminergic function of the adrenal medulla and myocardial adrenergic receptors, which may contribute to the development and maintenance of many of the hemodynamic and metabolic defects described in this animal model of diabetes mellitus.