Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation.
OBJECTIVE
Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS.


METHODS
Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME.


RESULTS
A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2).


CONCLUSIONS
These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.
First Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. xjzh42@nms.ac.jp
Xue-Jun
XJ
Zhang
Yasumi
Y
Katsuta
Toshio
T
Akimoto
Masaru
M
Ohsuga
Takumi
T
Aramaki
Teruo
T
Takano
D000818:Animals; D001652:Bile Ducts; D002196:Capillaries / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020065:Hepatopulmonary Syndrome / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D015995:Prevalence; D011651:Pulmonary Artery; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester