Effects of calcium channel blockers and hydralazine on epinephrine-induced hyperglycemia in vivo.
Effects of calcium channel blockers from structurally different classes and hydralazine on epinephrine-induced hyperglycemia were studied in vivo. Nifedipine (0.05-0.20 mg/kg, i.p.) and nicardipine (0.40-0.80 mg/kg, i.p.) markedly potentiated the epinephrine-induced hyperglycemia in a dose-dependent manner. In contrast to these dihydropyridine calcium channel blockers, verapamil and diltiazem did not significantly affect the epinephrine-induced hyperglycemia at doses of 0.10-1.0 mg/kg, i.p. At higher doses (10 mg/kg, i.p.), significant potentiation of epinephrine-induced hyperglycemia was observed by these non-dihydropyridine calcium channel blockers. Hydralazine also markedly increased the epinephrine-induced hyperglycemia. These calcium channel blockers and hydralazine had no significant effect on the basal plasma glucose levels at any dose used here. As judged from the rates of glucose disappearance (K values), dihydropyridines significantly impaired the glucose tolerance in much lower doses than those of non-dihydropyridines and hydralazine. Furthermore, epinephrine-induced impairment of glucose tolerance was markedly potentiated by these calcium channel blockers and hydralazine at doses which potentiated the epinephrine-induced hyperglycemia. These results suggest that, at least in part, the potentiation of epinephrine-induced hyperglycemia by dihydropyridines, non-dihydropyridines and hydralazine is related to the inhibition of peripheral glucose utilization produced by insulin.
Josai University, Faculty of Pharmaceutical Sciences, Group of Biochemical Pharmacology, Saitama, Japan.
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Ogihara
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005508:Food Deprivation / Q000502:physiology; D005951:Glucose Tolerance Test; D006830:Hydralazine / Q000494:pharmacology*; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006830:Hydralazine; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D004837:Epinephrine