Adrenalectomy potentiates the anti-inflammatory activity of a calcium channel blocker

Calcium movement is important in the activation of inflammatory cells. Prior studies have shown that calcium channel blockers (CCBs) inhibit carrageenan-induced paw edema in rats by acting at pituitary and hypothalamic levels. Here we evaluated the role of calcium channel blockers and their regulation via the hypothalamus-pituitary-adrenal (HPA) axis in acute and chronic models of rat paw inflammation, using both carrageenan (acute) and formalin (chronic) as inflammation inducers. Adrenalectomized (ADX) and intact Sprague Dawley rats (n = 4 per group) weighing 150-250 each were treated with an intraperitoneal injection of nifedipine (400 microg/kg) or vehicle. Edema was assessed plethysmometrically by evaluating paw volume changes. The results show a significant contradiction between acute and chronic inflammation data. In intact animals, nifedipine demonstrated a significant anti-inflammatory effect in the acute inflammatory model but not in the chronic model. In adrenal-ectomized animals, the anti-inflammatory effect of nifedipine was significantly enhanced both in acute and chronic models. We conclude that adrenalectomy plays a significant role in modulating the inflammatory pathway in the presence of calcium channel blockers.