Hypercholesterolemia promotes endothelial dysfunction in vitamin E- and selenium-deficient rats.
Abnormal regulation of local vascular tone occurs early in human and experimental atherosclerosis. Impaired endothelium-dependent vascular relaxations mediated by endothelium-derived relaxing factor are an important contributor to these abnormalities. Endothelium-derived relaxing factor is nitric oxide released as such or attached to a carrier molecule. Oxidized lipoproteins impede endothelium-derived relaxing factor-mediated responses in vitro. We designed in vivo experiments to determine whether hypercholesterolemia with and without deficiency of two endogenous lipid antioxidants, vitamin E and selenium, would result in endothelial dysfunction. Vitamin E and selenium deficiencies were induced in a group of hypertension-prone Dahl salt-sensitive rats fed a diet high in cholesterol (4%) but low in NaCl (0.5%) for 18 weeks. Two other groups of Dahl salt-sensitive rats received diets sufficient in vitamin E and selenium but containing either high or normal cholesterol levels (control group). Serum cholesterol levels increased approximately 10-fold in the two groups of rats fed high-cholesterol diets. Systolic blood pressure was 143 +/- 3 mm Hg in high-cholesterol/vitamin E- and selenium-sufficient rats and 142 +/- 5 mm Hg in high-cholesterol/vitamin E- and selenium-deficient rats (P = NS). Mild intimal thickening and occasional mononuclear cell infiltration were observed in both of these groups. Serum vitamin E levels were decreased, whereas serum thiobarbituric acid-reactive substances and exhaled pentane (two indicators of endogenous lipid oxidation) were significantly increased in high-cholesterol/vitamin E- and selenium-deficient rats compared with high-cholesterol/vitamin E- and selenium-sufficient rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Raij
L
L
Medical Research Service, Veterans Affairs Medical Center, Minneapolis, MN 55417.
Nagy
J
J
Coffee
K
K
DeMaster
E G
EG
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology*; D007213:Indomethacin / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D012643:Selenium / Q000172:deficiency* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology; D014811:Vitamin E Deficiency / Q000150:complications*
D014810:Vitamin E; D009599:Nitroprusside; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D002784:Cholesterol; D013482:Superoxide Dismutase; D012643:Selenium; D000109:Acetylcholine; D007213:Indomethacin