Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction.
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.
Liu
S F
SF
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Dewar
A
A
Crawley
D E
DE
Barnes
P J
PJ
Evans
T W
TW
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
D014409:Tumor Necrosis Factor-alpha; D000109:Acetylcholine; D010431:Pentoxifylline