Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

Publisher: Academic Press Country of Publication: United States NLM ID: 0165035 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9319 (Electronic) Linking ISSN: 00262862 NLM ISO Abbreviation: Microvasc Res Subsets: MEDLINE

Original Publication: New York, Academic Press.

Hemodynamics*/drug effects ; Splanchnic Circulation*/drug effects; Arterioles/*metabolism ; Heme Oxygenase (Decyclizing)/*metabolism ; Hypertension, Portal/*enzymology ; Liver Cirrhosis, Experimental/*enzymology ; Mesentery/*blood supply ; NF-E2-Related Factor 2/*metabolism; Animals ; Arterioles/drug effects ; Arterioles/physiopathology ; Carbon Tetrachloride ; Enzyme Inhibitors/pharmacology ; Heme Oxygenase (Decyclizing)/antagonists & inhibitors ; Hypertension, Portal/chemically induced ; Hypertension, Portal/drug therapy ; Hypertension, Portal/physiopathology ; Liver Cirrhosis, Experimental/chemically induced ; Liver Cirrhosis, Experimental/physiopathology ; Male ; Metalloporphyrins/pharmacology ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress ; Portal Pressure ; Protoporphyrins/pharmacology ; Rats, Sprague-Dawley ; Signal Transduction ; Up-Regulation ; Vascular Endothelial Growth Factor A/metabolism ; Vasoconstriction

Objective: We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats.
Methods: Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats.
Results: Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment.
Conclusions: The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats.
(Copyright © 2016 Elsevier Inc. All rights reserved.)

Keywords: Contractile response; Heme Oxygenase 1; Nuclear Factor-e2-related factor 2; Portal hypertension; Splanchnic hemodynamics

0 (Enzyme Inhibitors)
0 (Metalloporphyrins)
0 (NF-E2-Related Factor 2)
0 (Nfe2l2 protein, rat)
0 (Protoporphyrins)
0 (Vascular Endothelial Growth Factor A)
0 (vascular endothelial growth factor A, rat)
CL2T97X0V0 (Carbon Tetrachloride)
DIO3JT9G2P (tin protoporphyrin IX)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
EC 1.14.13.39 (Nos3 protein, rat)
EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
EC 1.14.14.18 (Hmox1 protein, rat)

Date Created: 20161228 Date Completed: 20171002 Latest Revision: 20201126

20240829

10.1016/j.mvr.2016.12.009

28025064