Nitric Oxide and Nitrogen Dioxide as Inducers of Acute Pulmonary Injury when Inhaled at Relatively High Concentrations for Brief Periods

Abstract

This investigation was undertaken in order to examine the pulmonary inflammatory response to nitric oxide (NO) relative to that of nitrogen dioxide (NO₂) when breathed at high concentrations for short durations. Croups of adult, male Fischer 344 rats were acutely exposed to 500–1500 pprn NO for 5–30 min using exposure protocols that minimized contaminating NO₂ concentrations (≤30 ppm) in the exposure system. Other groups of animals were acutely exposed to NO₂ delivered over a concentration range of 10–100 pprn for durations of 5–30 min. Rats exposed to filtered air only served as controls for the NO- and NO₂-rexposed groups. Twenty-four hours after the exposures, the animals were sacrificed for lung gravimetric and histopathologic analyses. Exposures of the rats to up to 1500 pprn NO for 15 min or 1000 ppm NO for 30 rnin produced no demonstrable increases in lung wet weights (LWW) or right cranial lobe dry weights (RCLDW). Likewise, such exposures did not result in any detectable histopathologic changes in the lungs. No significant increases in LWW or RCLDW were found following up to 30 min exposures to 10 or 25 ppm NO₂, or after exposures of the rats to 50 ppm NO₂ for 5 or 15 min durations. These lung gravimetric parameters, however, were significantly increased 24 h after 30 rnin exposures to 50 ppm NO₂ as well as after the 5–15 min exposures to 100 pprn NO₂ Histologic evidence of lung injury was observed following 30 min exposures to 25 ppm NO₂ but not at lesser exposure concentrations and times. The severity of lung injury following the higher NO₂ exposures was maximally expressed following the 75 min exposure to 700 ppm NO₂ The results of these studies indicate that NO, when inhaled at high concentrations for brief durations, does not cause an inflammatory response in the lung.