NITRIC-OXIDE INHALATION TRANSIENTLY ELEVATES PULMONARY LEVELS OF CGMP, INOS MESSENGER-RNA, AND TNF-ALPHA

The initial pulmonary vasodilation that occurs during nitric oxide (.N O) inhalation does not appear to be maintained chronically in many cas es. .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 decreasi ng levels of lipid peroxidation. It was hypothesized that the acute .N O-induced changes in cGMP, TNF-alpha, iNOS, and lipid peroxidation, al l of which may mediate vasodilation, are transient rather than sustain ed. Lungs from rats kept in chambers containing 6 parts/million .NO fo r 1 h, 1 day, or 1 wk were analyzed for levels of .NO-induced vasodila tory mediators. Pulmonary cGMP, iNOS mRNA, and TNF-alpha were increase d 1h after .NO exposure but decreased to control values at later times . Levels of malonyl dialdehyde, an indicator of lipid peroxidation, we re decreased at all times during .NO inhalation. As a whole, the data suggest that in lungs the vasodilatory mediators cGMP, iNOS, and TNF-a lpha are only acutely and transiently elevated during inhalation of .N O, consistent with the initially positive clinical response to inhaled .NO that deteriorates over time.