Nitric oxide inhalation transiently elevates pulmonary levels of cGMP, iNOS mRNA, and TNF-alpha.
The initial pulmonary vasodilation that occurs during nitric oxide (. NO) inhalation does not appear to be maintained chronically in many cases. . NO may acutely relax vascular smooth muscle by increasing levels of guanosine 3',5'-cyclic monophosphate (cGMP), tumor necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS) while decreasing levels of lipid peroxidation. It was hypothesized that the acute . NO-induced changes in cGMP, TNF-alpha, iNOS, and lipid peroxidation, all of which may mediate vasodilation, are transient rather than sustained. Lungs from rats kept in chambers containing 6 parts/million . NO for 1 h, 1 day, or 1 wk were analyzed for levels of . NO-induced vasodilatory mediators. Pulmonary cGMP, iNOS mRNA, and TNF-alpha were increased 1 h after . NO exposure but decreased to control values at later times. Levels of malonyl dialdehyde, an indicator of lipid peroxidation, were decreased at all times during . NO inhalation. As a whole, the data suggest that in lungs the vasodilatory mediators cGMP, iNOS, and TNF-alpha are only acutely and transiently elevated during inhalation of . NO, consistent with the initially positive clinical response to inhaled . NO that deteriorates over time.
Brady
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TC
Program in Integrated Toxicology, Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Crapo
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JD
Mercer
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D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000235:genetics; D000280:Administration, Inhalation; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*; D014664:Vasodilation
D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000262:Adenylyl Cyclases; D006152:Cyclic GMP