PMID- 11156858
OWN - NLM
STAT- MEDLINE
DCOM- 20010426
LR  - 20190831
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 21
IP  - 2
DP  - 2001 Feb
TI  - Flow-induced constriction in arterioles of hyperhomocysteinemic rats is due to 
      impaired nitric oxide and enhanced thromboxane A(2) mediation.
PG  - 233-7
AB  - Hyperhomocysteinemia (HHcy) is thought to promote arteriosclerosis and peripheral 
      arterial disease, in part by impairing the function of endothelium. Because 
      flow-induced dilation is mediated by the endothelium, we hypothesized that HHcy 
      alters this response by interfering with the synthesis/action of NO and 
      prostaglandins. Thus, changes in the diameter of isolated, pressurized (at 80 mm 
      Hg) gracilis skeletal muscle arterioles (diameter approximately 170 microm) from 
      control and methionine diet-induced HHcy rats were investigated with 
      videomicroscopy. Increases in intraluminal flow (from 0 to 25 microL/min) 
      resulted in dilations of control arterioles (maximum, 34+/-4 microm). In 
      contrast, increases in flow elicited constrictions of HHcy arterioles (-36+/-3 
      microm). In control arterioles, the NO synthase inhibitor 
      N:(omega)-nitro-L-arginine-methyl ester significantly attenuated (approximately 
      50%) dilation, whereas the additional administration of indomethacin, an 
      inhibitor of cyclooxygenase, eliminated flow-induced dilation. In the arterioles 
      of HHcy rats, flow-induced constriction was not affected by 
      N:(omega)-nitro-L-arginine-methyl ester, whereas it was abolished by indomethacin 
      or the prostaglandin H(2)/thromboxane A(2) (TXA(2)) receptor antagonist SQ 29,548 
      or the TXA(2) synthase inhibitor CGS 13,080. Thus, in HHcy, increases in 
      intraluminal flow elicit constrictions of skeletal muscle arterioles due to the 
      impaired NO and enhanced TXA(2) mediation of the response, alterations that 
      likely contribute to the development of peripheral arterial disease.
FAU - Bagi, Z
AU  - Bagi Z
AD  - Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
FAU - Ungvari, Z
AU  - Ungvari Z
FAU - Szollar, L
AU  - Szollar L
FAU - Koller, A
AU  - Koller A
LA  - eng
GR  - HL-43023/HL/NHLBI NIH HHS/United States
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.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 57576-52-0 (Thromboxane A2)
SB  - IM
MH  - Animals
MH  - Arterioles/metabolism/*physiopathology
MH  - Constriction, Pathologic
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/metabolism/physiopathology
MH  - Hyperhomocysteinemia/metabolism/*physiopathology
MH  - Male
MH  - Nitric Oxide/metabolism/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Thromboxane A2/metabolism/*physiology
EDAT- 2001/02/07 11:00
MHDA- 2001/05/11 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/05/11 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1161/01.atv.21.2.233 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2001 Feb;21(2):233-7. doi: 
      10.1161/01.atv.21.2.233.