NITROVASODILATOR REPLETION INCREASES TNF-ALPHA-INDUCED PULMONARY-EDEMA

We tested the hypothesis that nitrovasodilator repletion enhances tumo r necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs we re 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-alp ha-injected lungs, the thromboxane mimetic U-46619 (155 pmol/min) caus ed increases in pulmonary capillary pressure (Ppc) and lung weight (De lta W). In control lungs, the nitrovasodilator agonist S-nitroso-N-ace tyl-penicillamine (SNAP, 1 mu M) attenuated the U-46619-induced increa ses in Ppc. In lungs injected with TNF-alpha, SNAP had no effect on Pp c 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 repl etion enhances TNF-alpha-induced pulmonary edema, possibly via ONOO-.