Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in hyperhomocysteinemia: Possible role of peroxynitrite

Zsolt Bagi, Zoltan Ungvari, Akos Koller

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Abstract

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 ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 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 μm), 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 μm) 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 A2, resulting in arteriolar constriction.

Original languageEnglish (US)
Pages (from-to)28-33
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number1
DOIs
StatePublished - Jan 29 2002

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Hyperhomocysteinemia
Peroxynitrous Acid
Xanthine Oxidase
Constriction
Arterioles
Dilatation
Reactive Oxygen Species
Nitric Oxide
Uric Acid
Prostaglandins
Oxypurinol
Prostaglandin H2 Receptors Thromboxane A2
Reactive Nitrogen Species
Video Microscopy
Thromboxane A2
NADPH Oxidase
Nitric Oxide Synthase
Superoxides
Methionine
Catalase

Keywords

  • Arterioles
  • Flow-induced constriction
  • Homocysteine
  • Reactive oxygen species
  • Thromboxane A
  • Xanthine oxidase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in hyperhomocysteinemia: Possible role of peroxynitrite",
abstract = "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 ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 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 μm), 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 μm) 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 A2, resulting in arteriolar constriction.",
keywords = "Arterioles, Flow-induced constriction, Homocysteine, Reactive oxygen species, Thromboxane A, Xanthine oxidase",
author = "Zsolt Bagi and Zoltan Ungvari and Akos Koller",
year = "2002",
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doi = "10.1161/hq0102.101127",
language = "English (US)",
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AU - Ungvari, Zoltan

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N2 - 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 ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 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 μm), 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 μm) 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 A2, resulting in arteriolar constriction.

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 ≈ 170 μm) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 μm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 μm), which were abolished by the thromboxane A2 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 μm), 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 μm) 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 A2, resulting in arteriolar constriction.

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