title: Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets.
abstract: The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: C L
authors.initials: CL
authors.lastname: Chou
authors.forename: K
authors.initials: K
authors.lastname: Hsu
authors.forename: H I
authors.initials: HI
authors.lastname: Chen
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D055370:Lung Injury; D009637:Masoprocol / Q000494:pharmacology; D010477:Perfusion; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011654:Pulmonary Edema / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D001095:Arachidonic Acids; D016718:Arachidonic Acid; D009637:Masoprocol; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin