Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment

Zsolt Bagi, Csongor Csekó, Erika Tóth, Akos Koller

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: ∼170 μm) isolated from control (serum Hcy: 6 ± 1 μM), methionine diet-induced HHcy rats (4 wk, serum Hcy: 30 ± 6 μM), and HHcy rats treated with vitamin C, a known antioxidant (4 wk, 150 mg·kg body wt-1·day -1; serum Hcy: 32 ± 10 μM), were investigated. In vessels of HHcy rats, increases in intraluminal flow/WSS-induced dilations were converted to constrictions. Constrictions were unaffected by inhibition of NO synthesis by Nω-nitro-L-arginine methyl ester (L-NAME). Vitamin C treatment of HHcy rats reversed the WSS-induced arteriolar constrictions to L-NAME-sensitive dilations but did not affect control responses. Similar changes in responses were obtained for the calcium ionophore A-23187. In addition, diastolic and mean arterial blood pressure and serum 8-isoprostane levels (a marker of in vivo oxidative stress) were significantly elevated in rats with HHcy, changes that were normalized by vitamin C treatment. Taken together, our data show that in chronic HHcy long-term vitamin C treatment, by decreasing oxidative stress in vivo, enhanced NO bioavailability, restored the regulation of shear stress in arterioles, and normalized systemic blood pressure. Thus our study provides evidence that oxidative stress is an important in vivo mechanism that is primarily responsible for the development of endothelial dysregulation of WSS in HHcy.

Original languageEnglish (US)
Pages (from-to)H2277-H2283
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
DOIs
StatePublished - Dec 2003
Externally publishedYes

Keywords

  • Homocysteine
  • Nitric oxide
  • Thromboxane A power dissipation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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