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Comparative portal hypotensive effects as propranolol of vitamin D 3 treatment by decreasing intrahepatic resistance in cirrhotic rats
Author(s) -
Lee PeiChang,
Yang YingYing,
Lee WeiPing,
Lee KueiChuan,
Hsieh YunCheng,
Lee TzungYan,
Lin HanChieh
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12721
Subject(s) - medicine , propranolol , endocrinology , portal hypertension , portal venous pressure , angiotensin ii , vitamin d and neurology , calcitriol receptor , cirrhosis , receptor
Background and Aim Vitamin D 3 improves portal hypertension ( PH ) through the activation of vitamin D receptor ( VDR ) and calcium‐sensing receptor ( CaSR ) in cirrhotic rats. Propranolol is a non‐selective β‐blocker that is recommended for the treatment of PH . The present study aims to investigate the detail systemic and hepatic mechanisms of vitamin D 3 and propranolol, alone or in combination, in cirrhotic rats. Methods Common bile duct‐ligated and thioacetamide cirrhotic rats were treated with vehicle, propranolol (30 mg/kg/day), vitamin D 3 (0.5 μg/100 g/day, twice weekly), or propranolol + vitamin D 3 , separately. Results Significantly, propranolol and vitamin D 3 produced a similar magnitude of reduction in portal venous pressure ( PVP ) in cirrhotic rats through different mechanisms: whereas propranolol decreased PVP by reducing splanchnic hyperemia and cardiac index, vitamin D 3 decreased PVP by decreasing intrahepatic resistance ( IHR ). However, propranolol + vitamin D 3 did not further decrease PVP in cirrhotic rats. Notably, a marked decrease in hepatic VDR and CaSR expressions was noted in cirrhotic human/rat livers compared with non‐cirrhotic human/rat livers. In cirrhotic rats, vitamin D 3 administration decreasing IHR by inhibiting the renin–angiotensin system, hepatic oxidative stress, inflammation/fibrosis, angiotensin II ( ANGII ) production, CaSR ‐mediated ANGII hyperresponsiveness, ANGII ‐induced hepatic stellate cells contraction, and correcting hepatic endothelial dysfunction through upregulation of hepatic VDR , CaSR , and endothelial nitric oxide synthase expressions. Conclusion Chronic vitamin D 3 treatment alone results in comparative portal hypotensive effects as propranolol alone in cirrhotic rats with PH . Taken together, chronic vitamin D 3 administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side‐effects.

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