Altered vasoreactivity in lungs isolated from rats exposed to nitric oxide gas.
A rebound phenomenon (severe arterial desaturation and pulmonary vasoconstriction) has been observed in some patients with pulmonary hypertension after sudden discontinuation of nitric oxide (NO) inhalation therapy. The mechanism responsible for this phenomenon is unknown. It has recently been reported that NO synthase (NOS) can be inhibited by NO as a negative feedback mechanism. We therefore hypothesized that this rebound phenomenon might be attributable to reduced endogenous NO production due to inhibition of pulmonary endothelial NOS (eNOS) activity by inhaled NO. To test this hypothesis, vasoreactivities were compared in isolated perfused lungs from rats exposed to 40 ppm NO gas and room air for 2 days. The pressor responses to angiotensin II and hypoxia of lungs from rats exposed to NO were markedly potentiated and their depressor response to bradykinin was considerably impaired, whereas that to sodium nitroprusside was preserved, compared with the responses of those exposed to room air. This altered pulmonary vasoreactivity was also induced by lower concentrations of inhaled NO (as low as 1 ppm) and was completely reversed by discontinuation of NO inhalation for several (< 8) hours. The expression of eNOS mRNA by lungs isolated from rats exposed to 40 ppm NO and room air for 2 days did not differ. These results suggest that pulmonary endogenous NO production is reversibly reduced after relatively short-term NO inhalation, which probably inhibits eNOS activity directly. We speculate that reduced production of pulmonary endogenous NO by exogenous (inhaled) NO could be the mechanism responsible for this rebound phenomenon.
Oka
M
M
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Ohnishi
M
M
Takahashi
H
H
Soma
S
S
Hasunuma
K
K
Sato
K
K
Kira
S
S
D000280:Administration, Inhalation; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide