The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome.
OBJECTIVE
The hepatopulmonary syndrome occurs when intrapulmonary vasodilatation causes impaired arterial gas exchange in liver disease. The pathogenesis is poorly understood, although nitric oxide may be involved. Common bile duct ligation in the rat is a model of the hepatopulmonary syndrome, but no studies have evaluated NO in pulmonary vasodilatation in this model. The aim of this study was to determine whether NO contributes to intrapulmonary vasodilatation after bile duct ligation.


METHODS
Endothelial and inducible NO synthase (NOS) levels and localization and NO activity in pulmonary artery rings were assessed after bile duct ligation.


RESULTS
Pulmonary endothelial NOS levels increased and alveolar vascular staining was enhanced after bile duct ligation. No change in pulmonary inducible NOS levels or localization was detected. Increased endothelial NOS levels correlated with alterations in gas exchange and were accompanied by enhanced NO activity and a blunted response to phenylephrine, reversible by NOS inhibition, in pulmonary artery rings. Portal-vein-ligated animals, which do not develop intrapulmonary vasodilatation, had no changes in pulmonary NOS production or in NO activity in pulmonary artery rings.


CONCLUSIONS
NO, derived from pulmonary vascular endothelial NOS, contributes to intrapulmonary vasodilation in animal hepatopulmonary syndrome.
Fallon
M B
MB
Department of Internal Medicine, University of Alabama at Birmingham, USA.
Abrams
G A
GA
Luo
B
B
Hou
Z
Z
Dai
J
J
Ku
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003135:Common Bile Duct / Q000502:physiology / Q000601:surgery; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000209:etiology* / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008026:Ligation; D008107:Liver Diseases / Q000150:complications / Q000209:etiology* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D008171:Lung Diseases / Q000150:complications / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000503:physiopathology; D011651:Pulmonary Artery; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013577:Syndrome; D014664:Vasodilation / Q000502:physiology
D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester