Hypoxia inhibits nitric oxide synthesis in isolated rabbit lung.
Nitric oxide (NO.) has been proposed to modulate hypoxic vasoconstriction in the lung. The activity of nitric oxide synthase (NOS) can be inhibited by hypoxia because molecular oxygen is a necessary substrate for the enzyme. On the basis of this mechanism, we hypothesized that NOS activity has a key role in regulation of pulmonary vascular tone during hypoxia. We measured oxidation products of NO. released into the vasculature of isolated buffer-perfused rabbit lung ventilated with normoxic (21% O2), moderately hypoxic (5% O2), or anoxic (0% O2) gas using two methods. Mean PO2 in perfusate exiting the lung was 25 Torr during anoxic ventilation and 47 Torr during moderately hypoxic ventilation. We found that the amount of the NO. oxidation product nitrite released into the perfusate was suppressed significantly during ventilation with anoxic but not moderately hypoxic gas. During normoxic ventilation, nitrite release was inhibited by pretreatment with NG-monomethyl-L-arginine, a competitive inhibitor of NOS. To confirm that changes in nitrite concentration reflected changes in NO. release into the perfusate, major oxidation products of NO. (NOx) were assayed using a method for reduction of these products to NO. by vanadium(III) Cl. Release of NOx into the perfusate was suppressed by severe hypoxia (anoxic ventilation), and this effect was reversed by normoxia. Pulmonary vasoconstriction was observed during severe but not moderate hypoxia and was related inversely to the rate of nitrite release. These observations provide evidence that decreased NO. production contributes to the pulmonary vasoconstrictor response during severe hypoxia.
Kantrow
S P
SP
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Huang
Y C
YC
Whorton
A R
AR
Grayck
E N
EN
Knight
J M
JM
Millington
D S
DS
Piantadosi
C A
CA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D010100:Oxygen; D010313:Partial Pressure; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D026422:S-Nitrosoglutathione; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione; D010100:Oxygen