Addition of a TGR5 agonist to the ET-1-enriched perfusion buffer significantly reduced the ET-1-mediated rise in portal pressure as compared to vehicle containing perfusion buffer, indicating that TGR5 activation rapidly reduces ET-1-mediated portal hypertension (DMSO vs. TGR5 Ago/+1 nM ET-1 2.41 ± 0.26 cmH20 vs. 1.42 ± 0.18 cmH20 (1.7-fold decrease); DMSO vs. TGR5 Ago/+5 nM ET-1 2.9 ± 0.18 cmH20 vs. 1.89 ± 0.28 cmH20 (1.5-fold decrease), DMSO vs. TGR5 Ago/+15 nM ET-1 3.14 ± 0.15 cmH20 vs. 2.20 ± 0.3 cmH20 (1.4-fold decrease), (n = 5–6), p < 0.05) (Figure 7A). Here, EDN1 is linked to portal hypertension.