D. Johnson et al., N(G)-MONOMETHYL-L-ARGININE DOES NOT RESTORE LOSS OF HYPOXIC PULMONARYVASOCONSTRICTION INDUCED BY TNF-ALPHA, Journal of applied physiology, 75(2), 1993, pp. 618-625
Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, p
ulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction.
N(G)-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) produc
tion and prevents some systemic manifestations of TNF-alpha. We tested
using an isolated perfused canine lobe whether NO also mediates the p
ulmonary vascular effects of TNF-alpha. Total resistance (RT) was meas
ured during control and hypoxic ventilation over a 90-min period in si
x control lobes, five lobes treated with TNF-alpha (250 mug), six lobe
s treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (20
0 mg) + TNF-alpha (250 mug). In the control lobes RT increased (P < 0.
02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O . ml-1 . min dur
ing normoxic and hypoxic ventilation, respectively. RT decreased (P <
0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O
. ml-1 . min 30 min after TNF-alpha administration and did not further
change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O . ml-1 . m
in). L-NMMA pretreatment did not prevent the TNF-a-induced loss of hyp
oxic pulmonary vasoconstriction, with values of RT unchanged from norm
oxic (0.0541 +/- 0.0067 cmH2O . ml-1 . min) to hypoxic (0.0545 +/- 0.0
078 cmH2O . ml-1 . min) ventilation (P > 0.10) in the L-NMMA+TNF-alpha
group after TNF-alpha administration. We conclude that NO is not the
mediator responsible for the acute pulmonary vascular effects of TNF-a
lpha.