Role of adrenal steroids in the recovery from platelet activating factor challenge

Previous studies have shown that platelet activating factor (PAF) is a potentially important mediator of the acute hypotensive response to endotoxin. Direct administration of PAF to rodents induces profound hypotension and hemoconcentration; normal blood pressure recovery requires an intact sympatho-adrenal medullary system. Because adrenal steroids are also important in the physiological response to shock, the present studies were conducted to determine whether treatment of rodents with cortisone or surgical adrenalectomy would alter cardiovascular parameters during recovery from PAF challenge. When rats were pretreated daily for four days with cortisone (25 mg/kg, sc), the hypotensive response to PAF injection (2 micrograms/kg, iv) was significantly blunted (P less than 0.05). In adrenalectomized rats, recovery of blood pressure was significantly delayed (P less than 0.01). Heart rate was not significantly changed in the anesthetized rat preparation used. Pretreatment of mice with cortisone (25 mg/kg/day, sc, 4 days) completely blocked the increased vascular permeability, as measured by a rise in hematocrit induced by PAF (2 micrograms/kg, iv) (P less than 0.001). Adrenalectomized mice had a rise in hematocrit similar to that in sham-operated animals. Lung wet:dry weight ratio after PAF challenge was unaffected by cortisone or adrenalectomy. These results suggest that adrenal cortical glucocorticoids, in addition to adrenal medullary catecholamines, participate in the recovery from the cardiovascular alterations following PAF administration. Further, the efficacy of steroid pretreatment in shock models might involve, in part, the inhibition or reversal of PAF-induced cardiovascular alterations.