PMID- 19615686
OWN - NLM
STAT- MEDLINE
DCOM- 20100303
LR  - 20100128
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 208
IP  - 1
DP  - 2010 Jan
TI  - Cyclooxygenase-2 derived thromboxane A(2) and reactive oxygen species mediate 
      flow-induced constrictions of venules in hyperhomocysteinemia.
PG  - 43-9
LID - 10.1016/j.atherosclerosis.2009.06.014 [doi]
AB  - OBJECTIVE: Hyperhomocysteinemia (HHcy) has been shown to impair the endothelial 
      function of arterial vessels and promote thrombosis. There are no studies, 
      however, assessing the effects of HHcy on the vasomotor function of venules. We 
      hypothesized that HHcy activates pathophysiological mechanisms impairing 
      flow/shear stress-dependent responses of venules. METHODS AND RESULTS: Changes in 
      diameter of isolated gracilis muscle venules (diameter: approximately 250 microm 
      at 10 mmHg) of control and HHcy rats (induced by methionine diet for 5 weeks) to 
      increases in intraluminal flow were measured. Increases in flow elicited 
      dilations in control (at max.: 14+/-1%), but induced constrictions in HHcy 
      venules (at max.: -24+/-4%). Flow-induced constrictions in HHcy venules were 
      converted to dilations in the presence of the thromboxane A(2) (TxA(2)) receptor 
      (TP) antagonist SQ 29,548, which were then abolished by the simultaneous 
      administration of nitric oxide (NO) synthase inhibitor, L-NAME and non-selective 
      cyclooxygenase (COX) blocker, indomethacin. In addition, the selective COX-2 
      inhibitor NS 398 reversed flow-induced constrictions to dilations, which were 
      significantly decreased by additional COX-1 inhibitor, SC 560. Also, as compared 
      to controls, a SOD/CAT sensitive increased ethidium bromide fluorescence was 
      detected in HHcy small veins, indicating substantial production of reactive 
      oxygen species (ROS) in HHcy. Correspondingly, SOD/CAT diminished flow-induced 
      constrictions in venules of HHcy rats. CONCLUSIONS: In hyperhomocysteinemia 
      increases in flow/shear stress increases the production of COX-2-derived TxA(2), 
      and reactive oxygen species--that overcome the dilator effects of NO and 
      prostaglandins--eliciting constrictions in skeletal muscle venules; changes which 
      can increase vascular resistance and favor thrombus formation in the venular 
      circulation.
CI  - Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
FAU - Racz, Anita
AU  - Racz A
AD  - Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
FAU - Veresh, Zoltan
AU  - Veresh Z
FAU - Lotz, Gabor
AU  - Lotz G
FAU - Bagi, Zsolt
AU  - Bagi Z
FAU - Koller, Akos
AU  - Koller A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090618
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Reactive Oxygen Species)
RN  - 57576-52-0 (Thromboxane A2)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Cyclooxygenase 2/metabolism
MH  - Hyperhomocysteinemia/*metabolism/*physiopathology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - *Reactive Oxygen Species
MH  - Regional Blood Flow
MH  - Thromboxane A2/metabolism/*physiology
MH  - *Vasoconstriction
MH  - Venules/*physiopathology
EDAT- 2009/07/21 09:00
MHDA- 2010/03/04 06:00
CRDT- 2009/07/21 09:00
PHST- 2009/01/14 00:00 [received]
PHST- 2009/06/02 00:00 [revised]
PHST- 2009/06/08 00:00 [accepted]
PHST- 2009/07/21 09:00 [entrez]
PHST- 2009/07/21 09:00 [pubmed]
PHST- 2010/03/04 06:00 [medline]
AID - S0021-9150(09)00487-0 [pii]
AID - 10.1016/j.atherosclerosis.2009.06.014 [doi]
PST - ppublish
SO  - Atherosclerosis. 2010 Jan;208(1):43-9. doi: 
      10.1016/j.atherosclerosis.2009.06.014. Epub 2009 Jun 18.