title: Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction.
abstract: The effects of tumor necrosis factor (TNF) on hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent relaxation were examined in a blood-perfused rat lung preparation. Lungs from TNF-treated rats (0.26 mg/kg iv 12 h before experimentation) had a significantly greater HPV and a reduced vasorelaxant response to the endothelium-dependent vasodilator acetylcholine (ACh) but a similar vasorelaxant response to the endothelium-independent vasodilator nitroprusside compared with lungs from control rats (pretreated with 0.1 ml saline iv). Pentoxifylline (20 mg/kg iv and ip 20 min before administration of TNF) had no detectable effect on either HPV or ACh-induced relaxation but completely negated the augmentation on HPV and the inhibiting action on ACh-induced relaxation caused by TNF. The TNF effect on ACh relaxation was unaffected by pretreatment with L-arginine. These results indicate that TNF induces endothelial dysfunction and enhances HPV, effects that are inhibited by pentoxifylline.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: S F
authors.initials: SF
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Dewar
authors.forename: D E
authors.initials: DE
authors.lastname: Crawley
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010431:Pentoxifylline / Q000494:pharmacology; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011654:Pulmonary Edema / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000109:Acetylcholine; D010431:Pentoxifylline