EFFECT OF 48 HOURS OF NITRIC-OXIDE INHALATION ON PULMONARY VASOREACTIVITY IN RATS

Nitric oxide (NO) has been shown to down regulate its own synthesis in vitro. We tested the hypothesis that NO inhalation (30 ppm under norm oxic conditions) could decrease the release of endogenous endothelial NO, and thus alter pulmonary vasoreactivity. Pulmonary vasoreactivity was assessed in isolated perfused rat lungs immediately or 6 h after a 48 h NO inhalation period, and compared with a control group. NO inha lation resulted in an increase in pulmonary vasoconstrictor reactivity to angiotensine II and U-46619, a reduction in the potentiation by th e eNOS inhibitor L-NAME of the angiotensine II response, a decrease in endothelium-dependent vasodilation to arginine vasopressin, whereas n on-endothelium-dependent vasodilation to sodium nitroprusside remained unaltered. These alterations returned to control values in the group studied 6 h after the end of NO inhalation, and were not prevented by inhibition of the prostanoid synthesis, or by pretreatment with the en dothelin receptors antagonist Bosentan. These results indicate that NO inhalation over 2 d induces a reversible alteration of pulmonary vaso reactivity in relationship with a decrease in endogenous NO release. I nhibition of eNOS could be involved.