Interactions of tumor necrosis factor and granulocytes with pulmonary vascular resistance.
We studied the effects of endotoxin and tumor necrosis factor (TNF-alpha) on hypoxic pulmonary vasoconstriction (HPV) in 12 isolated perfused canine lung lobes. Group 1 lobes were perfused with whole blood, and group 2 lobes were perfused with granulocyte-depleted blood. All lobes were sequentially ventilated with control (35% O2) and hypoxic (3% O2) gas mixtures before and after receiving TNF-alpha. After TNF-alpha, group 2 lost HPV but group 1 retained HPV. After TNF-alpha, total pulmonary vascular resistance decreased in group 2 from 0.085 +/- 0.013 to 0.049 +/- 0.016 cmH2O.ml-1.min (P less than 0.05). We conclude that TNF-alpha acts as a pulmonary vascular vasodilator. In lobes perfused with whole blood, HPV is paradoxically preserved. We speculate that in the presence of cells rich in TNF-alpha receptors, i.e., granulocytes, the circulating levels of TNF-alpha are depressed and full expression of its vascular effects is blunted.
Mayers
I
I
Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
Johnson
D
D
Hurst
T
T
To
T
T
D000818:Animals; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity; D006098:Granulocytes / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha