PMID- 16143648
OWN - NLM
STAT- MEDLINE
DCOM- 20060123
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 290
IP  - 1
DP  - 2006 Jan
TI  - Vascular dysfunction produced by hyperhomocysteinemia is more severe in the 
      presence of low folate.
PG  - H181-91
AB  - Earlier we reported that dietary folate depletion causes hyperhomocysteinemia 
      (HHcy) and arterial dysfunction in rats (Symons JD, Mullick AE, Ensunsa JL, Ma 
      AA, and Rutledge JC. Arterioscler Thromb Vasc Biol 22: 772-780, 2002). Both HHcy 
      and low folate (LF) are risk factors for cardiovascular disease. Therefore, the 
      dysfunction we observed could have resulted from HHcy, LF, and/or their 
      combination (HHcy + LF). We tested the hypothesis that HHcy-induced vascular 
      dysfunction is more severe in the presence of LF. Four groups of rats consumed 
      diets for approximately 10 wk that produced plasma homocysteine (microM) and 
      liver folate (microg folate/g liver) concentrations, respectively, of 7 +/- 1 and 
      15 +/- 1 (Control; Con; n = 16), 17 +/- 2 and 15 +/- 2 (HHcy; n = 17), 10 +/- 1 
      and 8 +/- 1 (LF; n = 14), and 21 +/- 2 and 8 +/- 1 (HHcy + LF; n = 18). We 
      observed that maximal ACh-evoked vasorelaxation was greatest in aortas and 
      mesenteric arteries from Con rats vs. all groups. While the extent of dysfunction 
      was similar between LF and HHcy animals, it was less severe compared with 
      arteries from HHcy + LF rats. Maximal ACh-evoked vasorelaxation in coronary 
      arteries was not different between Con and LF rats, but both were greater than 
      HHcy + LF animals. In segments of aortas, 1) ACh-evoked vasorelaxation was 
      similar among groups after incubation with the nonenzymatic intracellular O2(-) 
      scavenger Tiron, 2) vascular O2(-) estimated using dihydroethidium staining was 
      greatest in HHcy + LF vs. all groups, and 3) tension development in response to 
      nitric oxide (NO) synthase inhibition was greatest in Con vs. all other groups. 
      We conclude that HHcy + LF evokes greater dysfunction than either HHcy alone 
      (aortas, mesentery) or LF alone (aortas, mesentery, coronary), likely by 
      producing more O2(-) within the vasculature and thereby reducing NO 
      bioavailability.
FAU - Symons, J David
AU  - Symons JD
AD  - College of Health, Univ. of Utah, Salt Lake City, UT, USA. 
      j.david.symons@hsc.utah.edu
FAU - Rutledge, John C
AU  - Rutledge JC
FAU - Simonsen, U
AU  - Simonsen U
FAU - Pattathu, Roshny A
AU  - Pattathu RA
LA  - eng
GR  - DK-35747/DK/NIDDK NIH HHS/United States
GR  - HL-55667/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20050902
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 169D1260KM (Nitroprusside)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AE28F7PNPL (Methionine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Diet
MH  - Endothelium, Vascular/*drug effects/pathology
MH  - Folic Acid Deficiency/complications/*physiopathology
MH  - Hyperhomocysteinemia/complications/*physiopathology
MH  - Male
MH  - Methionine/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitroprusside/pharmacology
MH  - Oxygen/metabolism
MH  - Rats
MH  - Vasodilation/*drug effects
MH  - omega-N-Methylarginine/pharmacology
EDAT- 2005/09/07 09:00
MHDA- 2006/01/24 09:00
CRDT- 2005/09/07 09:00
PHST- 2005/09/07 09:00 [pubmed]
PHST- 2006/01/24 09:00 [medline]
PHST- 2005/09/07 09:00 [entrez]
AID - 00765.2005 [pii]
AID - 10.1152/ajpheart.00765.2005 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H181-91. doi: 
      10.1152/ajpheart.00765.2005. Epub 2005 Sep 2.