Calcium channel blockers reduce inflammatory edema in the rat: Involvement of the hypothalamus-pituitary-adrenal axis

Objective: To evaluate the role of calcium channel blockers and their mechanisms of action on acute inflammation of rat paw. Material and Methods: The study was conducted using carrageenan-induced rat paw inflammation model. Two different doses of nifedipine and verapamil (25 and 400 μg/kg, i.p.) were used. Edema was assessed by calculating the volume changes and by extravasation of Evans blue dye. Results: Nifedipine reduced edema dose-dependently, whereas verapamil was effective only at low dose. Adrenalectomy prevented the effect of nifedipine and verapamil. With low dose of nifedipine 66% of antiinflammatory effect was observed. Pretreatment with α-helical corticotropin releasing factor (CRF 9-41), a corticotropin-releasing hormone (CRH) receptor antagonist, had the same effect as that of adrenalectomy for either doses of verapamil, but only the effect of low-dose nifedipine was prevented completely. Conclusion: Our data suggest that verapamil and nifedipine exerts a potent antiinflammatory action possibly through pituitary adrenocortical activation.