In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 88, No. 6 ( 2010-06), p. 636-643
Abstract:
Hepatic and circulating endothelin-1 (ET-1) are increased in patients with cirrhosis and in cirrhotic animals. However, the distinct roles of ET receptor subtypes ET A and ET B in cirrhosis and portal hypertension (PHT) have not been clearly elucidated. Thus, we studied the effects of selective ET-1 antagonists (ET A -ant or ET B -ant) and nonselective ET-1 antagonist (ET A/B -ant) on hepatic hemodynamics in cirrhotic rats. Liver fibrosis and PHT were induced by complete bile duct ligation (BDL) in rats. Two weeks after BDL or sham surgery, hemodynamic responses were measured during intraportal infusion of incremental doses of the following ET-ants: (i) BQ-123, (ii) BQ-788, and (iii) bosentan. After equilibration with vehicle, doses of ET-ants were infused for 30 min periods, and steady-state systemic and hepatic hemodynamics, portal venous pressure (PVP), and hepatic blood flow (HBF) were measured. BDL induced significant PHT and elevated concentrations of plasma ET-1 compared with sham. ET A -ant decreased PVP of cirrhotic rats but had no effect on sham, whereas ET B -ant increased PVP in sham but had no effect in BDL. Nonselective ET A/B -ant decreased PVP of BDL similarly to ET A -ant. Both ET A -ant and ET B -ant decreased local HBF, whereas a nonselective antagonist did not change HBF in sham; however no significant changes were observed in HBF of BDL rats with any of the antagonists. These findings suggest ET A activation contributes to PHT in cirrhotic rats, whereas ET B -mediated portal depressor effects are attenuated in cirrhotic rats compared with noncirrhotic rats.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2010
detail.hit.zdb_id:
2004356-9
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