The sinusoidal pressure during ischemia-reperfusion injury in perfused mouse liver pretreated with or without L-NAME.
BACKGROUND
Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver.


METHODS
Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT).


RESULTS
In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h.


CONCLUSIONS
Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.
Shibamoto
Toshishige
T
Department of Physiology, Kanazawa Medical University, Uchinada Ishikawa, Japan. shibamo@kanazawa-med.ac.jp
Ruan
Zonghai
Z
Cui
Sen
S
Liu
Wei
W
Zhao
Zhan-Sheng
ZS
Takano
Hiromichi
H
Kurata
Yasutaka
Y
Koizumi
Tomonobu
T
Kubo
Keishi
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006503:Hepatic Veins / Q000503:physiopathology; D008099:Liver / Q000098:blood supply*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D014655:Vascular Resistance; D014690:Venous Pressure
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000410:Alanine Transaminase; D019331:NG-Nitroarginine Methyl Ester