Different hepatic vascular response to noradrenaline and histamine between guinea-pig and rat.

AIM: Hepatic xenotransplantation from guinea-pig to rat has not been established. This failure is partly ascribed to differences in hepatic vascular characteristics between two species. However, the differences in hepatic vascular resistance distribution and responses to vasoconstrictors are not known. The present study was designed to determine basal levels of segmental vascular resistances and the responses to histamine and noradrenaline in isolated guinea-pig and rat livers. METHODS: The livers were haemoperfused (Hct 8.3%) via the portal vein at a constant flow. The sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. RESULTS: There was no significant difference in basal total hepatic vascular resistance (Rt) between two species, whereas Rpre in rat (69% of Rt) was significantly greater than that in guinea-pig (61% of Rt). The responses to noradrenaline were similar; Rpre increased in a greater magnitude than Rpost, and liver weight was reduced. However, the noradrenaline-induced increase in Rt was greater in rats than in guinea-pigs. In contrast, histamine increased predominantly Rpost over Rpre, and increased liver weight in guinea-pig, while it affected no haemodynamic variables in rat. CONCLUSION: There exist species differences in the hepatic vasculature between rat and guinea-pig. Basal pre-sinusoidal resistance in rat is greater than that in guinea-pig. Although noradrenaline predominantly contracts pre-sinusoidal vessels in both species, histamine causes predominant post-sinusoidal vasoconstriction in guinea-pig liver, while it has no vasoactive effects on rat liver.

Effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells.

AIM: To study the effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 (MMP-2) in hepatic stellate cells (HSC). METHODS: The expressions of MMP-2, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and membrane type matrix metalloproteinase-1 (MT1-MMP) in cultured rat HSC were detected by immunocytochemistry (ICC) and in situ hybridization (ISH). The contents of MMP-2 and TIMP-2 in culture supernatant were detected with ELISA and the activity of MMP-2 in supernatant was revealed by zymography. RESULTS: In the situation of hypoxia for 12h, the expression of MMP-2 protein was enhanced (hypoxia group positive indexes: 5.7 +/- 2.0, n=10; control: 3.2 +/- 1.0, n = 7; P<0.05), while TIMP-2 protein was decreased in HSC (hypoxia group positive indexes: 2.5 +/- 0.7, n = 10; control: 3.6 +/- 1.0, n = 7; P < 0.05), and the activity (total A) of MMP-2 in supernatant declined obviously (hypoxia group: 7.334 +/- 1.922, n = 9; control: 17.277 +/- 7.424, n = 11; P < 0.01). Compared the varied duration of hypoxia, the changes of expressions including mRNA and protein level as well as activity of MMP-2 were most notable in 6h group. The highest value(A(hypoxia)-A(control)) of the protein and the most intense signal of mRNA were in the period of hypoxia for 6h, along with the lowest activity of MMP-2. In the situation of hyperoxia for 12h, the contents (A(450)) of MMP-2 and TIMP-2 in supernatant were both higher than those in the control, especially the TIMP-2 (hyperoxia group: 0.0499 +/- 0.0144, n = 16; control: 0.0219 +/- 0.0098, n = 14; P < 0.01), and so was the activity of MMP-2 (hyperoxia group: 5.252 +/- 0.771, n = 14; control: 4.304 +/- 1.083, n = 12; P < 0.05), and the expression of MT1-MMP was increased. CONCLUSION: HSC is sensitive to the oxygen, hypoxia enhances the expression of MMP-2 and the effect is more marked at the early stage; hyperoxia mainly raises the activity of MMP-2.

Increased sinusoidal pressure is associated with early liver weight gain in ischemia-reperfusion injury in isolated perfused rat liver.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation. This could be caused by an increase in sinusoidal pressure, a determinant of hepatic transvascular fluid movement. We determined the role of sinusoidal pressure, assessed by triple vascular occlusion pressure (P(to)), in the I/R injury in isolated rat livers perfused with leukocyte-free diluted blood bivascularly via the portal vein and hepatic artery. MATERIALS AND METHODS: Ischemia was induced at room temperature by occlusion of either the inflow lines of the hepatic artery and portal vein (the open outflow group, n = 10) or both the inflow and the outflow (hepatic venous) lines (the closed outflow group, n = 10) for 1 h, followed by 1-h reperfusion in a recirculating manner. RESULTS: Liver weight in both groups increased biphasically after reperfusion; the initial peak occurred at 3 min and the second peak at 60 min. Immediately after reperfusion, P(to) peaked, followed by a gradual decline. The initial weight increase in groups combined was significantly and positively correlated with an increase in P(to) (r = 0.716, P = 0.0002), but the second peak was independent of P(to). Liver injury, assessed by perfusate levels of hepatic enzymes and reduced bile flow rate, was observed at 60 min after reperfusion in both groups. CONCLUSIONS: These findings suggest that increased sinusoidal pressure contributes to only the early liver weight gain after reperfusion in isolated perfused rat livers. The late weight gain may be presumably due to liver injury.