Contribution of type I NOS to expired gas NO and bronchial responsiveness in mice.
Nitric oxide (NO) can be measured in the expired gas of humans and animals, but the source of expired NO (F(E)NO) and the functional contribution of the various known isoforms of NO synthase (NOS) to the NO measured in the expired air is not known. F(E)NO was measured in the expired air of mice during mechanical ventilation via a tracheal cannula. F(E)NO was significantly higher in wild-type B6SV129J +/+ mice than in mice with a targeted deletion of type I (neural) NOS (nNOS, -/-) (6.3 +/- 0.9 vs. 3.9 +/- 0.4 parts/billion, P = 0.0345, for +/+ and -/- mice, respectively), indicating that approximately 40% of the NO in expired air in B6SV129 mice is derived from nNOS. Airway responsiveness to methacholine (MCh), assessed by the log of the effective dose of MCh for a doubling of pulmonary resistance from baseline (ED(200)R(L)), was significantly lower in the -/- nNOS mice than in the wild-type mice (logED(200)R(L), 2.24 +/- 0.07 vs. 2.51 +/- 0.06 microg/kg, respectively; P = 0.003). These findings indicate that nNOS significantly contributes to baseline F(E)NO and promotes airway hyperresponsiveness in the mouse.
De Sanctis
G T
GT
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Mehta
S
S
Kobzik
L
L
Yandava
C
C
Jiao
A
A
Huang
P L
PL
Drazen
J M
JM
D000818:Animals; D001921:Brain / Q000201:enzymology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D009569:Nitric Oxide / Q000032:analysis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012119:Respiration; D012121:Respiration, Artificial; D017384:Sequence Deletion
D007527:Isoenzymes; D016210:Methacholine Chloride; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase