PMID- 12869370
OWN - NLM
STAT- MEDLINE
DCOM- 20031224
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 285
IP  - 6
DP  - 2003 Dec
TI  - Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood 
      pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment.
PG  - H2277-83
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: approximately 170 microm) isolated from control (serum Hcy: 6 +/- 1 
      microM), methionine diet-induced HHcy rats (4 wk, serum Hcy: 30 +/- 6 microM), 
      and HHcy rats treated with vitamin C, a known antioxidant (4 wk, 150 mg. kg body 
      wt-1.day-1; serum Hcy: 32 +/- 10 microM), 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 N 
      omega-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.
FAU - Bagi, Zsolt
AU  - Bagi Z
AD  - Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Cseko, Csongor
AU  - Cseko C
FAU - Toth, Erika
AU  - Toth E
FAU - Koller, Akos
AU  - Koller A
LA  - eng
GR  - HL-46813/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030717
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Antioxidants)
RN  - 0 (F2-Isoprostanes)
RN  - 0 (Ionophores)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (S-nitro-N-acetylpenicillamine)
RN  - 27415-26-5 (8-epi-prostaglandin F2alpha)
RN  - 37H9VM9WZL (Calcimycin)
RN  - B7IN85G1HY (Dinoprost)
RN  - GNN1DV99GX (Penicillamine)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Arterioles/physiology
MH  - Ascorbic Acid/*pharmacology
MH  - Blood Pressure/*physiology
MH  - Calcimycin/pharmacology
MH  - *Dinoprost/*analogs & derivatives
MH  - F2-Isoprostanes/blood
MH  - Hyperhomocysteinemia/*drug therapy/metabolism/*physiopathology
MH  - Ionophores/pharmacology
MH  - Male
MH  - Muscle, Skeletal/blood supply
MH  - Nitric Oxide Donors/pharmacology
MH  - Oxidative Stress/drug effects/physiology
MH  - Penicillamine/*analogs & derivatives/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/physiology
MH  - Stress, Mechanical
MH  - Vascular Resistance/physiology
EDAT- 2003/07/19 05:00
MHDA- 2003/12/25 05:00
CRDT- 2003/07/19 05:00
PHST- 2003/07/19 05:00 [pubmed]
PHST- 2003/12/25 05:00 [medline]
PHST- 2003/07/19 05:00 [entrez]
AID - 00448.2003 [pii]
AID - 10.1152/ajpheart.00448.2003 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2277-83. doi: 
      10.1152/ajpheart.00448.2003. Epub 2003 Jul 17.