PMID- 12107099
OWN - NLM
STAT- MEDLINE
DCOM- 20020806
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 161
IP  - 1
DP  - 2002 Jul
TI  - Impaired nitric oxide-mediated flow-induced coronary dilation in 
      hyperhomocysteinemia: morphological and functional evidence for increased 
      peroxynitrite formation.
PG  - 145-53
AB  - Hyperhomocysteinemia (HHcy) is a newly recognized risk factor for myocardial 
      infarction, however, the effect of HHcy on endothelium-dependent flow-induced 
      dilation of coronary arteries is not known. Thus, changes in diameter of small 
      intramural coronary arteries (diameter, approximately 145 microm) isolated from 
      control rats and rats with methionine diet-induced HHcy were investigated by 
      videomicroscopy. Increases in intraluminal flow (from 0 to 40 microl/min) 
      elicited dilations of control vessels (maximum, 25 +/- 2 microm), responses that 
      were absent in HHcy arteries. The nitric oxide (NO) synthase inhibitor L-NAME 
      inhibited flow-induced dilation of control coronaries, whereas it had no effect 
      on responses of HHcy arteries. Dilations of control and HHcy arteries to the NO 
      donor sodium nitroprusside were not different. Responses to flow in HHcy coronary 
      arteries were unaffected by administration of L-arginine or the prostaglandin 
      H(2)/thromboxane A(2) receptor antagonist SQ 29,548. However, in the presence of 
      superoxide dismutase (plus catalase) or the superoxide scavenger Tiron increases 
      in flow elicited L-NAME-sensitive dilations of HHcy coronaries (maximum, 18 +/- 5 
      microm). Also, superoxide dismutase significantly reduced the enhanced superoxide 
      production of HHcy coronaries (measured by the lucigenin chemiluminescence 
      method). Single vessel Western blotting showed an increased tyrosine nitrosation 
      (a stable biomarker of tissue peroxynitrite formation) in HHcy coronaries. Also, 
      extensive prevalence of 3-nitrotyrosine immunoreactivity was observed in HHcy 
      coronaries that was confined primarily to the subendothelial layers of smooth 
      muscle. We propose that in HHcy an increased level of superoxide scavenges NO 
      forming peroxynitrite, which increases protein nitrosation. The reduced 
      bioavailability of NO impairs flow-induced dilations of coronary arteries, which 
      may contribute to the development of coronary atherosclerosis and ischemic heart 
      disease.
FAU - Ungvari, Zoltan
AU  - Ungvari Z
AD  - Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
FAU - Csiszar, Anna
AU  - Csiszar A
FAU - Bagi, Zsolt
AU  - Bagi Z
FAU - Koller, Akos
AU  - Koller A
LA  - eng
GR  - HL-46813/HL/NHLBI NIH HHS/United States
GR  - P01-1HL-43023/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.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Enzyme Inhibitors)
RN  - 11062-77-4 (Superoxides)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Coronary Circulation/drug effects/*physiology
MH  - Coronary Vessels/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Hyperhomocysteinemia/pathology/*physiopathology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/*physiology
MH  - Peroxynitrous Acid/biosynthesis/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Superoxides/metabolism
MH  - Tyrosine/*analogs & derivatives/metabolism
MH  - *Vasodilation
PMC - PMC1850707
EDAT- 2002/07/11 10:00
MHDA- 2002/08/07 10:01
PMCR- 2003/01/01
CRDT- 2002/07/11 10:00
PHST- 2002/07/11 10:00 [pubmed]
PHST- 2002/08/07 10:01 [medline]
PHST- 2002/07/11 10:00 [entrez]
PHST- 2003/01/01 00:00 [pmc-release]
AID - S0002-9440(10)64166-1 [pii]
AID - 3207 [pii]
AID - 10.1016/S0002-9440(10)64166-1 [doi]
PST - ppublish
SO  - Am J Pathol. 2002 Jul;161(1):145-53. doi: 10.1016/S0002-9440(10)64166-1.