Effects of calcium channel blockers and hydralazine on plasma glucose levels in streptozotocin-induced diabetic rats in vivo.
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 beta-adrenoceptor antagonist propranolol. In contrast, hydralazine markedly produced hyperglycemia, which was also inhibited by the combined administration of propranolol. The selective alpha 1-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. These results suggest that endogenous catecholamines are involved in the hydralazine-induced hyperglycemia through the interaction with beta-adrenoceptors in streptozotocin-diabetic rats in vivo.
Sunaga
K
K
Group of Biochemical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Ogihara
M
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000378:metabolism
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D002395:Catecholamines; D006584:Hexamethonium Compounds; D006830:Hydralazine; D011433:Propranolol; D009529:Nicardipine; D009543:Nifedipine; D011224:Prazosin; D010646:Phentolamine