title: Change in lipid profile and impairment of endothelium-dependent relaxation of blood vessels in rats after bile duct ligation.
abstract: Hyperlipidemia, a condition normally observed in cholestatic liver disease, is also a risk factor for the development of atherosclerosis. The relationship between the elevation of lipoproteins in cholestatic liver diseases and atherosclerosis formation has not been elucidated. In this study, we propose that the impairment of endothelium-dependent relaxation (EDR) of blood vessels in cholestatic liver diseases may lead to the development of atherosclerosis. Using bile duct ligation (BDL) in rats as a model, we examined the liver function, serum lipid profile, EDR and morphologic change of the aorta from both sham operated and BDL rats. Significant increases in liver and spleen weights, serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and the bilirubin level were observed in BDL rats. Upon bile duct ligation, the total and low-density lipoprotein cholesterol levels were increased but the high-density lipoprotein cholesterol and triglyceride levels were reduced. Less contractility and lowered response to acetylcholine-induced relaxation were found in aorta segments. In addition, the acetylcholine-induced relaxation was blocked by both L-NAME and 15 mM KCl. Our results suggest that both nitric oxide and endothelium-derived hyperpolarizing factor are important elements for the impairment of the EDR in BDL rats. In addition, a mild atrophy of the media of the aorta was detected in BDL rats. We conclude that the alterations of lipid profile and the mild atrophy of the media may lead to the impairment of EDR in the aorta in BDL rats, and these factors may potentiate the development of atherosclerosis.
authors.affiliation: Department of Internal Medicine, Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, A108 Chown Building, 753 McDermot Avenue, Manitoba, Winnipeg, Canada R3E 0W3.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Jenny Y
authors.initials: JY
authors.lastname: Jiang
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Xu
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Kroeger
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.forename: Hongqun
authors.initials: H
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.forename: Gerald Y
authors.initials: GY
authors.lastname: Minuk
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Choy
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D008055:Lipids / Q000097:blood*; D008106:Liver Cirrhosis, Experimental / Q000097:blood* / Q000150:complications; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009929:Organ Size; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D008055:Lipids; D011189:Potassium Chloride; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester