cholecalciferol and Hypertension--Portal

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 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 D₃ and propranolol, alone or in combination, in cirrhotic rats.. Common bile duct-ligated and thioacetamide cirrhotic rats were treated with vehicle, propranolol (30 mg/kg/day), vitamin D₃ (0.5 μg/100 g/day, twice weekly), or propranolol + vitamin D₃, separately.. 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 + 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 with non-cirrhotic human/rat livers. In cirrhotic rats, vitamin D₃ 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.. 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.

Topics: Adrenergic beta-Antagonists; Animals; Cholecalciferol; Disease Models, Animal; Drug Therapy, Combination; Humans; Hypertension, Portal; Liver Cirrhosis; Propranolol; Rats; Receptors, Calcitriol; Receptors, Calcium-Sensing; Treatment Outcome; Vascular Resistance