PMID- 11788457
OWN - NLM
STAT- MEDLINE
DCOM- 20020207
LR  - 20190901
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 22
IP  - 1
DP  - 2002 Jan
TI  - Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar 
      dilation to constriction in hyperhomocysteinemia: possible role of peroxynitrite.
PG  - 28-33
AB  - We hypothesized that in hyperhomocysteinemia (HHcy), flow-induced arteriolar 
      constriction is due to an enhanced generation of reactive oxygen and/or nitrogen 
      species, causing an impairment of nitric oxide (NO) and prostaglandin mediation 
      of the response. Changes in diameter of isolated, pressurized (at 80 mm Hg) 
      gracilis muscle arterioles (diameter approximately 170 microm) from control and 
      methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in 
      intraluminal flow (from 0 to 25 microL/min) resulted in NO- and 
      prostaglandin-mediated dilations of control arterioles (maximum, control, 30+/-4 
      microm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, 
      -32+/-3 microm), which were abolished by the thromboxane A(2) receptor blocker SQ 
      29,548. Intraluminal administration of superoxide dismutase plus catalase did not 
      affect flow-mediated dilations of control arterioles, but in HHcy arterioles, it 
      reversed the flow-induced constrictions to dilations (maximum 18+/-4 microm), 
      which were abolished by an NO synthase inhibitor. Flow-induced constrictions of 
      HHcy arterioles were prevented by the presence of the xanthine oxidase inhibitor 
      oxypurinol [but not by the NAD(P)H-oxidase inhibitor diphenyleneiodonium] and by 
      urate, a known peroxynitrite scavenger. Also, authentic peroxynitrite elicited 
      arteriolar constrictions (-31+/-8 microm) that were eliminated by urate and SQ 
      29,548. Thus, we suggest that in HHcy, xanthine oxidase-derived superoxide 
      scavenges NO released to flow, forming peroxynitrite, which promotes release of 
      thromboxane A(2), resulting in arteriolar constriction.
FAU - Bagi, Zsolt
AU  - Bagi Z
AD  - Department of Pathophysiology, Semmelweis University, H-1445, Budapest, Hungary.
FAU - Ungvari, Zoltan
AU  - Ungvari Z
FAU - Koller, Akos
AU  - Koller A
LA  - eng
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  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Hydrazines)
RN  - 0 (Prostaglandins)
RN  - 0 (Reactive Oxygen Species)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 88SD2J5ZNX (SQ 29548)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Arterioles/drug effects/physiopathology
MH  - Bridged Bicyclo Compounds, Heterocyclic
MH  - Catalase/pharmacology
MH  - Fatty Acids, Unsaturated
MH  - Hydrazines/pharmacology
MH  - Hyperhomocysteinemia/metabolism/*physiopathology
MH  - Male
MH  - Muscle, Skeletal/blood supply
MH  - Nitric Oxide/*physiology
MH  - Peroxynitrous Acid/pharmacology
MH  - Prostaglandins/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/*metabolism
MH  - Superoxide Dismutase/pharmacology
MH  - Thromboxane A2/antagonists & inhibitors/*physiology
MH  - Vasoconstriction/*physiology
MH  - Vasodilation/*physiology
EDAT- 2002/01/15 10:00
MHDA- 2002/02/08 10:01
CRDT- 2002/01/15 10:00
PHST- 2002/01/15 10:00 [pubmed]
PHST- 2002/02/08 10:01 [medline]
PHST- 2002/01/15 10:00 [entrez]
AID - 10.1161/hq0102.101127 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):28-33. doi: 10.1161/hq0102.101127.