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

Abstract：

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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

De Gottardi A,Shaw S,Sägesser H,Reichen J

doi

10.1016/s0168-8278(00)80303-7

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

733-7

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168827800803037

journal_volume

33

pub_type

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