Hyperthermia induced in rabbits by organic calcium antagonists

Verapamil, nifedipine and cinnarizine, when injected intracerebroventricularly (ICV), induced a rise in core temperature related to the dose of the drug and accompanied by vasoconstriction of the ear vascular bed. On the contrary, the calcium channel activator BAY-K-8644, structurally related to nifedipine, elicited a dose-related hypothermic response which was accompanied by vasodilatation. The delay in onset of verapamil-induced hyperthermia was reduced by pretreating the animals with a dose of acetylsalicylic acid (ASA) which antagonized fever induced by E. coli endotoxin. BAY-K-8644 was shown to partially antagonize E. coli endotoxin-induced fever. These findings indicate that neurons responsible for temperature control are a target of organic calcium antagonists and suggest that calcium metabolism is of primary importance in the function of these cells.