Comparative portal hypotensive effects as propranolol of vitamin D3 treatment by decreasing intrahepatic resistance in cirrhotic rats. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Lee, Pei‐Chang; Yang, Ying‐Ying; Lee, Wei‐Ping; Lee, Kuei‐Chuan; Hsieh, Yun‐Cheng; Lee, Tzung‐Yan; Lin, Han‐Chieh
• Is Part Of: Journal of gastroenterology and hepatology. Volume 30:Issue 3(2015:Mar.)
• Page Start: 628
• Page End: 637
• Publication Date: 2015-03
• Subjects: Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.12721
• Languages: English
• ISSNs: 0815-9319

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jgh12721-sec-0001" sec-type="section"> <title>Background and Aim</title> <p>Vitamin D<sub>3</sub> 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<sub>3</sub> and propranolol, alone or in combination, in cirrhotic rats.</p> </sec> <sec id="jgh12721-sec-0002" sec-type="section"> <title>Methods</title> <p>Common bile duct‐ligated and thioacetamide cirrhotic rats were treated with vehicle, propranolol (30 mg/kg/day), vitamin D<sub>3</sub> (0.5 μg/100 g/day, twice weekly), or propranolol + vitamin D<sub>3</sub>, separately.</p> </sec> <sec id="jgh12721-sec-0003" sec-type="section"> <title>Results</title> <p>Significantly, propranolol and vitamin D<sub>3</sub> 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<sub>3</sub> decreased PVP by decreasing intrahepatic resistance (IHR). However, propranolol + vitamin D<sub>3</sub> 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<sub>3</sub> 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.</p> </sec> <sec id="jgh12721-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Chronic vitamin D<sub>3</sub> treatment alone results in comparative portal hypotensive effects as propranolol alone in cirrhotic rats with PH. Taken together, chronic vitamin D<sub>3</sub> administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side‐effects.</p> </sec> </abstract>