Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro

Abstract

Objective: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro. Design and setting: Prospective study in a university pediatric intensive care ward and research laboratory. Patients and materials: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro. Interventions: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro. Measurements and results: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 ± 0.24 cmH2O/torr (mean ± SEM) to 4.90 ± 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 ± 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 ± 0.17 cmH2O/torr; p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 ± 4.0 μM/min) than in control cells (37.6 ± 7.0 μM/min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 ± 10.0 ♂/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot). Conclusion: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.