Аннотация:Portal hypertension (PH) develops in various liver diseases and is associated with impaired blood supply to this organ. The aim of this study was to compare the effects of PH on the vessels supplying blood to the liver, the portal vein and hepatic artery. PH was modeled in male C57Bl/6J mice by ligation of the common bile duct, while animals in the control group were sham-operated. Three weeks later, the animals were euthanized, and their organs (liver and spleen) were weighed. Blood samples were collected for biochemical analysis, and liver tissue samples were taken for gene expression studies using quantitative PCR. Additionally, the portal vein and hepatic artery were isolated to examine their responses in an isometric myograph or to analyze gene expression. The development of hepatic pathology was validated by an increase in liver mass (relative to body weight), alterations in blood biochemical parameters (elevated ALT and alkaline phosphatase activity, increased levels of total bilirubin, direct bilirubin, and total cholesterol), and upregulation of fibrosis marker genes (Acta2 andMmp9). The splenic mass in mice with bile duct ligation was increased compared to the control group,consistent with PH. The portal vein in PH mice exhibited an enhanced maximal contractile response to U46619 (a thromboxane A2 receptor agonist) along with the reduced sensitivity to this agonist, decreased acetylcholine-mediated relaxation, and increased sensitivity to nitric oxide. Reduced contractile responses of the vein to ATP were also observed, accompanied by upregulated expression of genes encoding proteins of the purinergic signaling system (Panx1, P2rx1, P2rx4, and Nt5e). No significant functional changes were detected in the hepatic artery of PH mice. These findings indicate the predominant involvement of the portal vein in the early stages of PH and highlight its key role in vasculardysfunction during liver pathologies.
