Journal of Applied Physiology
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J Appl Physiol 80: 2151-2155, 1996;
8750-7587/96 $5.00
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Journal of Applied Physiology, Vol 80, Issue 6 2151-2155, Copyright © 1996 by American Physiological Society

ARTICLES

Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema

A. Johnson and T. J. Ferro
Research Service, Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York, USA.

We tested the hypothesis that nitrovasodilator repletion enhances tumor necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs were isolated from control guinea pigs or 4 h after the intraperitoneal injection of TNF-alpha (1.60 x 10(5) U/kg). In the control and TNF-alpha-injected lungs, the thromboxane mimetic U-46619 (155 pmol/min) caused increases in pulmonary capillary pressure (Ppc) and lung weight (delta W). In control lungs, the nitrovasodilator agonist S-nitroso-N-acetyl-penicillamine (SNAP, 1 microM) attenuated the U-46619-induced increases in Ppc. In lungs injected with TNF-alpha, SNAP had no effect on Ppc and increased delta W. The peroxynitrite (ONOO-) scavenger urate (35 mM) prevented the TNF-alpha +SNAP-induced increases in Ppc and delta W. In addition, chemically synthesized ONOO- (4.0 mM) enhanced U-46619-induced increases in delta W. The data indicate that nitric oxide repletion enhances TNF-alpha-induced pulmonary edema, possibly via ONOO-.


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