PMID- 18448615
OWN - NLM
STAT- MEDLINE
DCOM- 20080903
LR  - 20211020
IS  - 0363-6119 (Print)
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Linking)
VI  - 295
IP  - 1
DP  - 2008 Jul
TI  - Chronic diet-induced hyperhomocysteinemia impairs eNOS regulation in mouse 
      mesenteric arteries.
PG  - R59-66
LID - 10.1152/ajpregu.00833.2007 [doi]
AB  - Hyperhomocysteinemia (HHcy) impairs endothelium-dependent vasodilation by 
      increasing reactive oxygen species, thereby reducing nitric oxide (NO.) 
      bioavailability. It is unclear whether reduced expression or function of the 
      enzyme that produces NO., endothelial nitric oxide synthase (eNOS), also 
      contributes. It is also unclear whether resistance vessels that utilize both 
      NO.and non-NO.vasodilatory mechanisms, undergo alteration of non-NO.mechanisms in 
      this condition. We tested these hypotheses in male C57BL/6 mice with chronic HHcy 
      induced by 6-wk high methionine/low-B vitamin feeding (Hcy: 89.2 +/- 49.0 microM) 
      compared with age-matched controls (Hcy: 6.6 +/- 1.9 microM), using first-order 
      mesenteric arteries. Dilation to ACh (10(-9)-10(-4) M) was measured in isolated, 
      cannulated, and pressurized (75 mmHg) arteries with and without 
      N(G)-nitro-l-arginine methyl ester (l-NAME) (10(-4) M) and/or indomethacin 
      (10(-5) M) to test endothelium-dependent dilation and non-NO.-dependent dilation, 
      respectively. The time course of dilation to ACh (10(-4) M) was examined to 
      compare the initial transient dilation due to non-NO., non-prostacyclin mechanism 
      and the sustained dilation due to NO.. These experiments indicated that 
      endothelium-dependent dilation was attenuated (P < 0.05) in HHcy arteries due to 
      downregulation of only NO.-dependent dilation. Western blot analysis indicated 
      significantly less (P < 0.05) basal eNOS and phospho-S1179-eNOS/eNOS in 
      mesenteric arteries from HHcy mice but no difference in phospho-T495-eNOS/eNOS. 
      S1179 eNOS phosphorylation was also significantly less in these arteries when 
      stimulated with ACh ex vivo or in situ. Real-time PCR indicated no difference in 
      eNOS mRNA levels. In conclusion, chronic diet-induced HHcy in mice impairs eNOS 
      protein expression and phosphorylation at S1179, coincident with impaired 
      NO.-dependent dilation, which implicates dysfunction in eNOS post-transcriptional 
      regulation in the impaired endothelium-dependent vasodilation and microvascular 
      disease that is common with HHcy.
FAU - Looft-Wilson, Robin C
AU  - Looft-Wilson RC
AD  - College of William and Mary, Department of Kinesiology, Williamsburg, Virginia 
      23187-8795, USA. rlooft@wm.edu
FAU - Ashley, Blair S
AU  - Ashley BS
FAU - Billig, Janelle E
AU  - Billig JE
FAU - Wolfert, Madeline R
AU  - Wolfert MR
FAU - Ambrecht, Lindsay A
AU  - Ambrecht LA
FAU - Bearden, Shawn E
AU  - Bearden SE
LA  - eng
GR  - 1-R15-HL082647-01/HL/NHLBI NIH HHS/United States
GR  - AHA0435389T/PHS HHS/United States
GR  - AHA0765259U/PHS HHS/United States
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080430
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Vasoconstrictor Agents)
RN  - 0 (Vasodilator Agents)
RN  - 169D1260KM (Nitroprusside)
RN  - 1WS297W6MV (Phenylephrine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Chronic Disease
MH  - *Diet
MH  - Endothelium/metabolism
MH  - Enzyme Induction/physiology
MH  - Hyperhomocysteinemia/etiology/*metabolism
MH  - Male
MH  - Mesenteric Arteries/drug effects/*enzymology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitrates/blood
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Nitrites/blood
MH  - Nitroprusside/pharmacology
MH  - Phenylephrine/pharmacology
MH  - Vasoconstrictor Agents/pharmacology
MH  - Vasodilator Agents/pharmacology
PMC - PMC2494800
EDAT- 2008/05/02 09:00
MHDA- 2008/09/04 09:00
PMCR- 2009/07/01
CRDT- 2008/05/02 09:00
PHST- 2008/05/02 09:00 [pubmed]
PHST- 2008/09/04 09:00 [medline]
PHST- 2008/05/02 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 00833.2007 [pii]
AID - R-00833-2007 [pii]
AID - 10.1152/ajpregu.00833.2007 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R59-66. doi: 
      10.1152/ajpregu.00833.2007. Epub 2008 Apr 30.