Dual action of nitric oxide on airway plasma leakage.
In the rat, plasma leakage in various vascular beds, including the whole lung, occurs after administration of lipopolysaccharide (LPS). LPS-induced microvascular plasma leakage in many organs is associated with an enhanced formation of nitric oxide (NO) after the induction of nitric oxide synthase (iNOS). However, there is limited information concerning the relationship between NO and plasma leakage into the airways. LPS (10 mg/kg, intravenously) caused a significant leakage of Evans blue dye, a marker of microvascular permeability, at 240 min in the trachea which was inhibited by the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, intravenously), or dexamethasone (1 mg/kg, intravenously). This effect was paralleled by an increase in calcium-independent iNOS activity, assessed by measuring the conversion of radiolabeled L-arginine to L-citrulline, in LPS-treated animals. In contrast, L-NAME significantly increased plasma leakage in the trachea of vehicle-treated rats and this effect was inhibited by indomethacin. These results suggest that under "physiological" conditions endogenous NO suppresses plasma leakage but when iNOS is expressed the increased production of NO enhances plasma leakage. These findings may implicate a role for NO in the maintenance of airway function and in the inflammatory process occurring in diseases such as asthma, where iNOS is known to be expressed.
Bernareggi
M
M
National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Mitchell
J A
JA
Barnes
P J
PJ
Belvisi
M G
MG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000098:blood supply*
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester