title: Vitamin E supplementation reverses renal altered vascular reactivity in chronic bile duct-ligated rats.
abstract: An altered vascular reactivity is an important manifestation of the hemodynamic and renal dysfunction during liver cirrhosis. Oxidative stress-derived substances and nitric oxide (NO) have been shown to be involved in those alterations. In fact, both can affect vascular contractile function, directly or by influencing intracellular signaling pathways. Nevertheless, it is unknown whether oxidative stress contributes to the impaired systemic and renal vascular reactivity observed in cirrhosis. To test this, we evaluated the effect of vitamin E supplementation (5,000 IU/kg diet) on the vasoconstrictor and vasodilator responses of isolated perfused kidneys and aortic rings of rats with cirrhosis induced by bile duct ligation (BDL), and on the expression of renal and aortic phospho-extracellular regulated kinase 1/2 (p-ERK1/2). BDL induced a blunted renal vascular response to phenylephrine and ACh, while BDL aortic rings responded less to phenylephrine but normally to ACh. Cirrhotic rats had higher levels of oxidative stress-derived substances [measured as thiobarbituric acid-reactive substances (TBARS)] and NO (measured as urinary nitrite excretion) than controls. Vitamin E supplementation normalized the renal hyporesponse to phenylephrine and ACh in BDL, although failed to modify it in aortic rings. Furthermore, vitamin E decreased levels of TBARS, increased levels of NO, and normalized the increased kidney expression of p-ERK1/2 of the BDL rats. In conclusion, BDL rats showed a blunted vascular reactivity to phenylephrine and ACh, more pronounced in the kidney and reversed by vitamin E pretreatment, suggesting a role for oxidative stress in those abnormalities.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alcaraz
authors.forename: D
authors.initials: D
authors.lastname: Iyú
authors.forename: N M
authors.initials: NM
authors.lastname: Atucha
authors.forename: J
authors.initials: J
authors.lastname: García-Estañ
authors.forename: M C
authors.initials: MC
authors.lastname: Ortiz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000503:physiopathology; D001652:Bile Ducts / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008026:Ligation / Q000009:adverse effects; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014810:Vitamin E; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester