Abstract <p>Portal hypertension (PH) develops in various liver diseasesand is associated with impaired blood supply to this organ. Theaim of this study was to compare the effects of PH on the vesselssupplying blood to the liver, the portal vein and hepatic artery.PH was modeled in male C57Bl/6J mice by ligation of the common bileduct, while animals in the control group were sham-operated. Threeweeks later, the animals were euthanized, and their organs (liverand spleen) were weighed. Blood samples were collected for biochemicalanalysis, and liver tissue samples were taken for gene expressionstudies using quantitative PCR. Additionally, the portal vein andhepatic artery were isolated to examine their responses in an isometricmyograph or to analyze gene expression. The development of hepatic pathologywas validated by an increase in liver mass (relative to body weight),alterations in blood biochemical parameters (elevated ALT and alkalinephosphatase activity, increased levels of total bilirubin, directbilirubin, and total cholesterol), and upregulation of fibrosismarker genes (<i>Acta2</i> and <i>Mmp9</i>). The splenic mass in mice withbile duct ligation was increased compared to the control group, consistentwith PH. The portal vein in PH mice exhibited an enhanced maximalcontractile response to U46619 (a thromboxane A2 receptor agonist)along with the reduced sensitivity to this agonist, decreased acetylcholine-mediatedrelaxation, and increased sensitivity to nitric oxide. Reduced contractile responsesof the vein to ATP were also observed, accompanied by upregulatedexpression of genes encoding proteins of the purinergic signalingsystem (<i>Panx1</i>, <i>P2rx1</i>, <i>P2rx4</i>,and <i>Nt5e</i>). No significant functionalchanges were detected in the hepatic artery of PH mice. These findingsindicate the predominant involvement of the portal vein in the earlystages of PH and highlight its key role in vascular dysfunctionduring liver pathologies.</p>