Thromboxane receptor stimulation/inhibition and perfusion redistribution after acute lung injury.
Perfusion redistribution (PR) after acute oleic acid (OA) lung injury may be the result of changes in the tissue concentration ratio of thromboxane (Tx) and prostacyclin (A. H. Stephenson et al. J. Appl. Physiol. 73: 2126-2134, 1992). We tested this hypothesis by determining whether the Tx mimetic U-46619 would mimic PR caused by cyclooxygenase inhibition with meclofenamate and whether the Tx receptor antagonist ONO-3708 would inhibit PR even in the presence of meclofenamate. Measurements of regional pulmonary blood flow (PBF) and lung water concentration were made with the nuclear medicine imaging technique of positron emission tomography. Measurements were made at baseline and 2 h after OA. At baseline, the spatial distribution of PBF was similar in all experimental groups. Two hours after OA, fractional PBF was reduced to the edematous lung in all groups given OA, but the magnitude of change was greater in those groups receiving meclofenamate or U-46619 compared with the change in the group given OA only. Thus, although the Tx mimetic produced the same amount of PR as meclofenamate, Tx inhibition did not prevent PR after meclofenamate. Therefore, the ratio of Tx to prostacyclin per se is not the critical determinant of PR.
Schuster
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DP
Department of Internal Medicine, Washington University Medical School, St. Louis, Missouri.
Sandiford
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P
Stephenson
A H
AH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000276:immunology / Q000378:metabolism; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D015633:Extravascular Lung Water / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D008469:Meclofenamic Acid / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000633:toxicity; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011654:Pulmonary Edema / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013929:Thromboxane B2 / Q000276:immunology / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D009829:Oleic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D019301:Oleic Acid; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C049855:ONO 3708