Nitric oxide inhalation transiently elevates pulmonary levels of cGMP, iNOS mRNA, and TNF-a

Brady, Todd C., James D. Crapo, and Robert R. Mercer. Nitric oxide inhalation transiently elevates pulmonary levels of cGMP, iNOS mRNA, and TNF-a. Am. J. Physiol. 275 (Lung Cell. Mol. Physiol. 19): L509–L515, 1998.— The initial pulmonary vasodilation that occurs during nitric oxide (zNO) inhalation does not appear to be maintained chronically in many cases. zNO may acutely relax vascular smooth muscle by increasing levels of guanosine 38,58-cyclic monophosphate (cGMP), tumor necrosis factor (TNF)-a, and inducible nitric oxide synthase (iNOS) while decreasing levels of lipid peroxidation. It was hypothesized that the acute zNO-induced changes in cGMP, TNF-a, iNOS, and lipid peroxidation, all of which may mediate vasodilation, are transient rather than sustained. Lungs from rats kept in chambers containing 6 parts/million zNO for 1 h, 1 day, or 1 wk were analyzed for levels of zNO-induced vasodilatory mediators. Pulmonary cGMP, iNOS mRNA, and TNF-a were increased 1 h after zNO exposure but decreased to control values at later times. Levels of malonyl dialdehyde, an indicator of lipid peroxidation, were decreased at all times during zNO inhalation. As a whole, the data suggest that in lungs the vasodilatory mediators cGMP, iNOS, and TNF-a are only acutely and transiently elevated during inhalation of zNO, consistent with the initially positive clinical response to inhaled zNO that deteriorates over time.