Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt.
Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS.
Nagasaka
Hironori
H
Division of Metabolism, Chiba Children's Hospital, Chiba 2666-0007, Japan. nagasa-hirono@k2.dion.ne.jp
Okano
Yoshiyuki
Y
Aizawa
Madoka
M
Miida
Takashi
T
Yorifuji
Tohru
T
Tajima
Go
G
Sakura
Nobuo
N
Takatani
Tomozumi
T
Sanayama
Yoshitami
Y
Sugamoto
Kenji
K
Mayumi
Mitsufumi
M
Kobayashi
Kunihiko
K
Hirano
Kenichi
K
Takayanagi
Masaki
M
Tsukahara
Hirokazu
H
D000596:Amino Acids / Q000097:blood; D000641:Ammonia / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001808:Blood Vessels / Q000503:physiopathology*; D002675:Child, Preschool; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D011168:Portal System / Q000002:abnormalities*
D000596:Amino Acids; D019332:Endothelin-1; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D000641:Ammonia; D001120:Arginine