Ambrosentan (BSF 208075) sodium is a selective and oral effective antagonist of ET type A receptor ( ETAR ).

Ambrisentan sodium, an endothelin type A receptor antagonist [1], promotes Nrf2 activation. It mitigates the increase in endothelial permeability observed in BMEC monolayers after 24 hours of hypoxia, compared to a vehicle control. However, this protective effect of Ambrisentan is negated when BMEC are pre-treated with siRNA targeting Nrf2 [2].

In the study, Ambrisentan treatment resulted in a notably lower hepatic hydroxyproline content compared to the control (18.0 μg/g±6.1 μg/g vs 33.9 μg/g±13.5 μg/g liver, P=0.014). Furthermore, assessments of hepatic fibrosis using Sirius red staining and the evaluation of areas positive for α-smooth muscle actin—a marker of hepatic stellate cell activation—revealed significant reductions in the Ambrisentan group (0.46%±0.18% vs 1.11%±0.28%, P=0.0003; and 0.12%±0.08% vs 0.25%±0.11%, P=0.047, respectively). Additionally, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced by 60% and 45%, respectively, in the Ambrisentan-treated group. It's important to note that Ambrisentan sodium's effect on inflammation, steatosis, and endothelin-related mRNA expression in the liver was not significant between groups. The findings suggest that Ambrisentan sodium mitigates hepatic fibrosis progression through the inhibition of hepatic stellate cell activation and a decrease in procollagen-1 and TIMP-1 gene expression, without influencing inflammation or steatosis.