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

Research output: Contribution to journalArticle

55 Scopus citations

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 - 2002
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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