Abstract
Effects of calcium channel blockers from structurally different classes and hydralazine on plasma glucose levels were examined in streptozotocin-induced diabetic rats in vivo. Non-dihydropyridine calcium channel blockers (verapamil, diltiazem, 1.0-10 mg/kg, i.p.) did not significantly affect the basal plasma glucose level, and dihydropyridine calcium channel blockers (nifedipine, 0.1-0.3 mg/kg, i. p.; nicardipine, 0.35-0.70 mg/kg, i.p.) caused mild hyperglycemia, which was blocked by the administration of the β-adrenoceptor antagonist propranolol. In contrast, hydralazine markedly produced hyperglycemia, which was also inhibited by the combined administration of propranolol. The selective α1-adrenoceptor antagonist prazosin greatly potentiated the hydralazine-induced hyperglycemia. Isoproterenol alone showed hyperglycemia similar to that of hydralazine. Hexamethonium (40 mg/kg, i.p.) a ganglionic blocker, blocked the hydralazine - induced hyperglycemia. There was a negative correlation between the hyperglycemic effect and the blood pressure lowering effect by different doses of hydralazine in streptozotocin-diabetic rats, but not in normal rats. There results suggest that endogenous catecholamines are involved in the hydralazine-induced hyperglycemia through the interaction with β-adrenoceptors in streptozotocin-diabetic rats in vivo.
