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Vitamin D3 treatment has comparative portal hypotensive effects as propranolol by decreasing intrahepatic resistance in cirrhotic rats.
MedLine Citation:
PMID:  25187428     Owner:  NLM     Status:  Publisher    
BACKGROUND & AIM: Vitamin D3 improves portal hypertension (PH) through the activation of vitamin D receptor (VDR) and calcium sensing receptor (CaSR) in cirrhotic rats. Propranolol is a nonselective β-blocker that is recommended for the treatment of PH. The present study aims to investigate the detail systemic and hepatic mechanisms of vitamin D3 and propranolol, alone or in combination, in cirrhotic rats.
METHODS: Common bile duct-ligated (BDL) and thioacetamide (TAA) cirrhotic rats were treated with vehicle, propranolol ( .day(-1) ), vitamin D3 (0.5μg.100g(-1) .day(-1) , twice weekly), or propranolol+ vitamin D3 , separately.
RESULTS: Significantly, propranolol and vitamin D3 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 D3 decreased PVP by decreasing intrahepatic resistance (IHR). However, propranolol plus vitamin D3 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 to non-cirrhotic human/rat livers. In cirrhotic rats, vitamin D3 administration decreasing IHR by inhibiting the renin-angiotensin system, hepatic oxidative stress, inflammation/fibrosis, ANGII production, CaSR-mediated angiotensin II (ANGII) hyper-responsiveness, ANGII-induced hepatic stellate cells contraction, and correcting hepatic endothelial dysfunction through up-regulation of hepatic VDR, CaSR and eNOS expressions.
CONCLUSION: Chronic vitamin D3 treatment alone results in comparative portal hypotensive effects as propranolol alone in cirrhotic rats with PH. Taken together, chronic vitamin D3 administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side effects.
Pei-Chang Lee; Ying-Ying Yang; Wei-Ping Lee; Kuei-Chuan Lee; Yun-Cheng Hsieh; Tzung-Yan Lee; Han-Chieh Lin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-4
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  -     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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This article is protected by copyright. All rights reserved.
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