Type A, but not type B, endothelin receptor antagonists significantly decrease portal pressure in portal hypertensive rats

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 (ETA-selective), A-192621 (ETB-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 ETB blocked group. In contrast, ETA 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 preand post-stenotic portal vein; p<0.0025). Conclusions: Oral administration of an ETA antagonist ameliorated portal hypertension; we suggest that long-term therapy of portal hypertension with selective ETA antagonists may be more beneficial than mixed antagonists.