Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model.
This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) (n = 8 piglets/group). A control group of healthy pigs (n = 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B(2) (TxB(2)), PGF(2alpha), and 6-keto-PGF(1alpha). Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB(2) and PGF(2alpha) increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen in endotoxemic piglets given INO only. We conclude that the rebound response to INO discontinuation is related to COX products.
Chen
Luni
L
Department of Medical Sciences, Clinical Physiology, University Hospital, SE-751 85 Uppsala, Sweden.
He
Hao
H
Fernandez Mondejar
Enrique
E
Hedenstierna
Göran
G
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000280:Administration, Inhalation; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000097:blood; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000473:pathology; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D009994:Osmolar Concentration; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012772:Shock, Septic / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases