Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema.
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-.
Johnson
A
A
Research Service, Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York, USA.
Ferro
T J
TJ
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide