Effects of ambient pressure on pulmonary nitric oxide

Abstract

Airway nitric oxide (NO) has been proposed to play a role in the development of high-altitude pulmonary edema. We undertook a study of the effects of acute changes of ambient pressure on exhaled and alveolar NO in the range 0.5–4 atmospheres absolute (ATA, 379–3,040 mmHg) in eight healthy subjects breathing normoxic nitrogen-oxygen mixtures. On the basis of previous work with inhalation of low-density helium-oxygen gas, we expected facilitated backdiffusion and lowered exhaled NO at 0.5 ATA and the opposite at 4 ATA. Instead, the exhaled NO partial pressure (PeNO) did not differ between pressures and averaged 1.21 ± 0.16 (SE) mPa across pressures. As a consequence, exhaled NO fractions varied inversely with pressure. Alveolar estimates of the NO partial pressure differed between pressures and averaged 88 ( P = 0.04) and 176 ( P = 0.009) percent of control (1 ATA) at 0.5 and 4 ATA, respectively. The airway contribution to exhaled NO was reduced to 79% of control ( P = 0.009) at 4 ATA. Our finding of the same PeNO at 0.5 and 1 ATA is at variance with previous findings of a reduced PeNO with inhalation of low-density gas at normal pressure, and this discrepancy may be due to the much longer durations of low-density gas breathing in the present study compared with previous studies with helium-oxygen breathing. The present data are compatible with the notion of an enhanced convective backtransport of NO, compensating for attenuated backdiffusion of NO with increasing pressure. An alternative interpretation is a pressure-induced suppression of NO formation in the airways.