The following is the abstract of the article discussed in the subsequent letter:

Worrall, Neil K., Kathy Chang, Wanda S. LeJeune, Thomas P. Misko, Patrick M. Sullivan, T. Bruce Ferguson, Jr., and Joseph R. Williamson. TNF- causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H2565-H2574, 1997.Tumor necrosis factor (TNF-) and nitric oxide (NO) are important vasoactive mediators of septic shock. This study used a well-characterized quantitative permeation method to examine the effect of TNF- and NO on systemic vascular barrier function in vivo, without confounding endotoxemia, hypotension, or organ damage. Our results showed 1) TNF- reversibly increased albumin permeation in the systemic vasculature (e.g., lung, liver, brain, etc.); 2) TNF- did not affect hemodynamics or blood flow or cause significant tissue injury; 3) pulmonary vascular barrier dysfunction was associated with increased lung water content and impaired oxygenation; 4) TNF- caused inducible nitric oxide synthase (iNOS) mRNA expression in the lung and increased in vivo NO production; 5) selective inhibition of iNOS with aminoguanidine prevented TNF--induced lung and liver vascular barrier dysfunction; 6) aminoguanidine prevented increased tissue water content in TNF--treated lungs and improved oxygenation; and 7) nonselective inhibition of NOS with N^G-monomethyl-L-arginine increased vascular permeation in control lungs and caused severe lung injury in TNF--treated animals. We conclude that 1) TNF- reversibly impairs vascular barrier integrity through NO-dependent and -independent mechanisms; 2) nonselective NOS inhibition increased vascular barrier dysfunction and caused severe lung injury, whereas selective inhibition of iNOS prevented impaired endothelial barrier integrity and pulmonary dysfunction; and 3) selective inhibition of iNOS may be beneficial in treating increased vascular permeability that complicates endotoxemia and cytokine immunotherapy.