Ibuprofen attenuates cardiopulmonary dysfunction by modifying vascular tone in endotoxemia

Ibuprofen, a cyclooxygenase inhibitor, improves pulmonary and cardiovascula r injury in endotoxemia, We studied the mechanism of the beneficial effects of ibuprofen in relation to production of inflammatory mediators which inf luence vascular tone in endotoxemia. Rats were randomly assigned to one of three groups: (1) control, (2) endotoxemia alone; and (3) ibuprofen pretrea tment and endotoxemia. Plasma and lung lavage concentrations of tumor necro sis factor, thromboxane B-2 (TXB2), leukotriene (LT) C-4,D-4,E-4 and nitric oxide (NO) were determined over a 2 h period. Pretreatment with ibuprofen resulted in increased survival, and attenuation of pulmonary and cardiovasc ular dysfunction when compared to the rats receiving endotoxin alone. The m arked elevation in plasma TXB2 concentration in endotoxemic rats was preven ted by pretreatment with ibuprofen. Similarly, pretreatment with ibuprofen prevented the decrease in lung lavage NO levels in endotoxemic rats. The im proved survival and cardiopulmonary protection in endotoxemic rats pretreat ed with ibuprofen appears to be related to decreased thromboxane production and preservation of endothelial production of nitric oxide.