Protective effect of chronic vitamin C treatment on endothelial function of apolipoprotein E-deficient mouse carotid artery

Takuya Matsumoto, Livius V. D'Uscio, Daihiko Eguchi, Masahiko Akiyama, Leslie A. Smith, Zvonimir S Katusic

Research output: Contribution to journalArticle

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Abstract

Endothelium-dependent relaxations are impaired in carotid artery of apolipoprotein E-deficient (apoE-/-) mice. This impairment seems to be due to increased formation of superoxide anions and inactivation of endothelial nitric oxide (NO). In the present study, we tested hypothesis that chronic treatment with vitamin C may prevent endothelial dysfunction by increasing release of NO from endothelial cells. C57BL/6 and apoE-/- mice were treated for 26 weeks with Western-type fat diet with and without 1% vitamin C. Vasomotor function of isolated carotid arteries was studied by video dimension analyzer. Expression of endothelial NO synthase (eNOS) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) protein were evaluated by Western blotting. Levels of cGMP and cAMP were measured by radioimmunoassay. In apoE-/- mice, vitamin C significantly augmented relaxations to acetylcholine (10-9-10-5 mol/l), but did not affect relaxations to NO donor diethylammonium-(Z)-1-(N,N-diethyl-amino) diazen-1-1,2-diolate (DEA-NONOate; 10-9-10-5 mol/l). In contrast, vitamin C reduced relaxations to acetyl-choline and DEA-NONOate in C57BL/6 mice. Interestingly, vitamin C significantly increased basal cGMP levels in C57BL/6 mice but did not affect cGMP formation in apoE-/-. Vitamin C treatment did not affect expression of eNOS protein, whereas elevated expression of PECAM-1 protein in apoE-/- mice was returned to normal level. Our findings demonstrate that chronic treatment with vitamin C prevents endothelial dysfunction of carotid artery induced by hyper-cholesterolemia. This effect seems to be mediated by preservation of NO bioavailability in endothelial cells.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume306
Issue number1
DOIs
StatePublished - Jul 1 2003

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Apolipoproteins E
Carotid Arteries
Ascorbic Acid
CD31 Antigens
Nitric Oxide
Inbred C57BL Mouse
Endothelial Cells
Proteins
Nitric Oxide Donors
Nitric Oxide Synthase Type III
Choline
Nitric Oxide Synthase
Superoxides
Biological Availability
Acetylcholine
Endothelium
Radioimmunoassay
Western Blotting
Fats
Diet

ASJC Scopus subject areas

  • Pharmacology

Cite this

Protective effect of chronic vitamin C treatment on endothelial function of apolipoprotein E-deficient mouse carotid artery. / Matsumoto, Takuya; D'Uscio, Livius V.; Eguchi, Daihiko; Akiyama, Masahiko; Smith, Leslie A.; Katusic, Zvonimir S.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 306, No. 1, 01.07.2003, p. 103-108.

Research output: Contribution to journalArticle

Matsumoto, Takuya ; D'Uscio, Livius V. ; Eguchi, Daihiko ; Akiyama, Masahiko ; Smith, Leslie A. ; Katusic, Zvonimir S. / Protective effect of chronic vitamin C treatment on endothelial function of apolipoprotein E-deficient mouse carotid artery. In: Journal of Pharmacology and Experimental Therapeutics. 2003 ; Vol. 306, No. 1. pp. 103-108.
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