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

The initial pulmonary vasodilation that occurs during nitric oxide (.NO) inhalation does not appear to be maintained chronically in many cases. .NO may acutely relax vascular smooth muscle by increasing levels of guanosine 3',5'-cyclic monophosphate (cGMP), tumor necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS) while decreasing levels of lipid peroxidation. It was hypothesized that the acute .NO-induced changes in cGMP, TNF-alpha, 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 .NO for 1 h, 1 day, or 1 wk were analyzed for levels of .NO-induced vasodilatory mediators. Pulmonary cGMP, iNOS mRNA, and TNF-alpha were increased 1h after .NO exposure but decreased to control values at later times. Levels of malonyl dialdehyde, an indicator of lipid peroxidation, were decreased at all times during .NO inhalation. As a whole, the data suggest that in lungs the vasodilatory mediators cGMP, iNOS, and TNF-alpha are only acutely and transiently elevated during inhalation of .NO, consistent with the initially positive clinical response to inhaled .NO that deteriorates over time.