Biomaterial Database

Effects of cyclooxygenase and lipoxygenase inhibition on lung fluid balance after thrombin. 1983

R Bizios, and F L Minnear, and H van der Zee, and A B Malik

We examined the roles of the cyclooxygenase and lipoxygenase pathways in the alterations in lung fluid and protein exchange after pulmonary microembolism. Infusion of alpha-thrombin (T) (55 +/- 13 U/kg) immediately increased mean pulmonary arterial pressure (Ppa) and mean pulmonary vascular resistance (PVR), but both Ppa and PVR waned with time after T. Cyclooxygenase inhibition with either indomethacin or ketoprofen produced sustained increases in Ppa and PVR. The initial increases in Ppa in the cyclooxygenase-inhibited groups (CI) were matched to the control group by administering greater amounts of T. In the control group, T rapidly increased pulmonary lymph flow (Qlym) by two- to threefold, and this was associated with a steady increase in lymph-to-plasma protein concentration ratio (L/P). In contrast, in cyclooxygenase-inhibited (CI) groups, Qlym increased gradually to greater levels than in the control group, and L/P did not change. The effect on lung vascular permeability was determined by inflating a left atrial balloon catheter to raise pulmonary capillary pressure (Pc). An increase in Pc after T in the control group further increased Qlym and did not change L/P, whereas the increase in Pc after T in CI groups further increased Qlym and decreased L/P, indicating that cyclooxygenase inhibition prevented the increase in permeability. We determined whether lipoxygenase activation contributed to the increase in Qlym in CI groups by examining the effects of BW755C, an inhibitor of both cyclooxygenase and lipoxygenase pathways. BW755C resulted in the same increase in Qlym after T as in the control group, but the increase in Qlym was associated with a decrease in L/P. Therefore, inhibition of both pathways prevented the permeability increase and the greater increase in Qlym. The results indicate that cyclooxygenase and lipoxygenase pathways contribute to the increases in pulmonary transvascular fluid and protein fluxes after thrombin.

UI	MeSH Term	Description	Entries
D007213	Indomethacin	A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.	Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007660	Ketoprofen	An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.	Benzoylhydratropic Acid,19,583 RP,2-(3-Benzoylphenyl)propionic Acid,Alrheumat,Alrheumum,Orudis,Profenid,RP-19583,RP 19583,RP, 19,583,RP19583
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013917	Thrombin	An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.	Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D014882	Water-Electrolyte Balance	The balance of fluid in the BODY FLUID COMPARTMENTS; total BODY WATER; BLOOD VOLUME; EXTRACELLULAR SPACE; INTRACELLULAR SPACE, maintained by processes in the body that regulate the intake and excretion of WATER and ELECTROLYTES, particularly SODIUM and POTASSIUM.	Fluid Balance,Electrolyte Balance,Balance, Electrolyte,Balance, Fluid,Balance, Water-Electrolyte,Water Electrolyte Balance
D015772	4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine	A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.	BW-755C,BW755C,BW 755C
D016859	Lipoxygenase Inhibitors	Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.	5-Lipoxygenase Inhibitor,Lipoxygenase Inhibitor,12-Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors,Arachidonate 12-Lipoxygenase Inhibitors,Arachidonate 15-Lipoxygenase Inhibitors,Arachidonate 5-Lipoxygenase Inhibitors,Inhibitors, Lipoxygenase,12 Lipoxygenase Inhibitors,12-Lipoxygenase Inhibitors, Arachidonate,15 Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors, Arachidonate,5 Lipoxygenase Inhibitor,5 Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors, Arachidonate,Arachidonate 12 Lipoxygenase Inhibitors,Arachidonate 15 Lipoxygenase Inhibitors,Arachidonate 5 Lipoxygenase Inhibitors,Inhibitor, 5-Lipoxygenase,Inhibitor, Lipoxygenase,Inhibitors, 12-Lipoxygenase,Inhibitors, 15-Lipoxygenase,Inhibitors, 5-Lipoxygenase,Inhibitors, Arachidonate 12-Lipoxygenase,Inhibitors, Arachidonate 15-Lipoxygenase,Inhibitors, Arachidonate 5-Lipoxygenase
D016861	Cyclooxygenase Inhibitors	Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.	Cyclo-Oxygenase Inhibitor,Cyclooxygenase Inhibitor,Prostaglandin Endoperoxide Synthase Inhibitor,Prostaglandin Endoperoxide Synthase Inhibitors,Prostaglandin Synthase Inhibitor,Prostaglandin Synthase Inhibitors,Prostaglandin Synthesis Antagonist,Prostaglandin Synthesis Antagonists,Cyclo-Oxygenase Inhibitors,Inhibitors, Cyclo-Oxygenase,Inhibitors, Cyclooxygenase,Inhibitors, Prostaglandin Synthase,Inhibitors, Prostaglandin-Endoperoxide Synthase,Antagonist, Prostaglandin Synthesis,Antagonists, Prostaglandin Synthesis,Cyclo Oxygenase Inhibitor,Cyclo Oxygenase Inhibitors,Inhibitor, Cyclo-Oxygenase,Inhibitor, Cyclooxygenase,Inhibitor, Prostaglandin Synthase,Inhibitors, Cyclo Oxygenase,Inhibitors, Prostaglandin Endoperoxide Synthase,Synthase Inhibitor, Prostaglandin,Synthesis Antagonist, Prostaglandin