Background/aim: Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats.
Methods: Four groups of 7 male Sprague-Dawley rats were administered orally ABT-627 (ET(A)-selective), A-192621 (ET(B)-selective), or A-182086 (non-selective), with the fourth group serving as control. On the 3rd day after beginning treatment animals underwent PPVL. On the 11th day hemodynamics were studied and portal vein ET-1 was measured.
Results: In the control group portal pressure was 13.4+/-SD 0.2 mmHg; this increased to 14.9+/-1.8 (p<0.05) in the ET(B) blocked group. In contrast, ET(A) blockade improved portal hypertension (11.7+/-1.1, p<0.05), while the treatment with the non-selective antagonist had no effect (12.3+/-0.7 n.s.). Mean arterial pressure was not significantly affected by any treatment. Portal vein ET-1 was increased in all groups compared to controls; this increase was limited to the pre-stenotic area (79+/-43 vs 194+/-76 in the pre- and post-stenotic portal vein; p<0.0025).
Conclusions: Oral administration of an ET(A) antagonist ameliorated portal hypertension; we suggest that long-term therapy of portal hypertension with selective ET(A) antagonists may be more beneficial than mixed antagonists.