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

Abstract

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)-α, and inducible nitric oxide synthase (iNOS) while decreasing levels of lipid peroxidation. It was hypothesized that the acute ⋅ NO-induced changes in cGMP, TNF-α, 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-α were increased 1 h 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-α are only acutely and transiently elevated during inhalation of ⋅ NO, consistent with the initially positive clinical response to inhaled ⋅ NO that deteriorates over time.