Ibuprofen attenuates cardiopulmonary dysfunction by modifying vascular tone in endotoxemia.
Ibuprofen, a cyclooxygenase inhibitor, improves pulmonary and cardiovascular injury in endotoxemia. We studied the mechanism of the beneficial effects of ibuprofen in relation to production of inflammatory mediators which influence vascular tone in endotoxemia. Rats were randomly assigned to one of three groups: (1) control, (2) endotoxemia alone; and (3) ibuprofen pretreatment and endotoxemia. Plasma and lung lavage concentrations of tumor necrosis factor, thromboxane B2 (TXB2), leukotriene (LT) C4,D4,E4 and nitric oxide (NO) were determined over a 2 h period. Pretreatment with ibuprofen resulted in increased survival, and attenuation of pulmonary and cardiovascular dysfunction when compared to the rats receiving endotoxin alone. The marked elevation in plasma TXB2 concentration in endotoxemic rats was prevented by pretreatment with ibuprofen. Similarly, pretreatment with ibuprofen prevented the decrease in lung lavage NO levels in endotoxemic rats. The improved survival and cardiopulmonary protection in endotoxemic rats pretreated with ibuprofen appears to be related to decreased thromboxane production and preservation of endothelial production of nitric oxide.
Heidemann
S M
SM
Department of Pediatrics, Children's Hospital of MI, Wayne State University School of Medicine, Detroit 48201, USA.
Ofenstein
J P
JP
Sarnaik
A P
AP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D007052:Ibuprofen / Q000627:therapeutic use*; D015289:Leukotrienes / Q000097:blood; D008168:Lung / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D013929:Thromboxane B2 / Q000097:blood; D014661:Vasoconstriction
D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D009569:Nitric Oxide; D013929:Thromboxane B2; D007052:Ibuprofen