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

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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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
StatePublished - Dec 1 2003
Externally publishedYes

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Hyperhomocysteinemia
Ascorbic Acid
Oxidative Stress
Blood Pressure
Constriction
Dilatation
Nitric Oxide
8-epi-prostaglandin F2alpha
NG-Nitroarginine Methyl Ester
Arterioles
Serum
Arterial Pressure
Calcium Ionophores
Calcimycin
Methionine
Biological Availability
Reactive Oxygen Species
Antioxidants
Diet

Keywords

  • Homocysteine
  • Nitric oxide
  • Thromboxane A power dissipation

ASJC Scopus subject areas

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

Cite this

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title = "Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment",
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.",
keywords = "Homocysteine, Nitric oxide, Thromboxane A power dissipation",
author = "Zsolt Bagi and Csongor Csek{\'o} and Erika T{\'o}th and Akos Koller",
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volume = "285",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
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T1 - Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment

AU - Bagi, Zsolt

AU - Csekó, Csongor

AU - Tóth, Erika

AU - Koller, Akos

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

KW - Homocysteine

KW - Nitric oxide

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M3 - Article

VL - 285

JO - American Journal of Physiology - Heart and Circulatory Physiology

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