Reoxygenation-induced constriction in murine coronary arteries. The role of endothelial NADPH oxidase (gp91phox) and intracellular superoxide

John Q. Liu, Igor N. Zelko, Rodney J. Folz

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Previous work suggests that superoxide mediates hypoxia/reoxygenation (H/R)-induced constriction of isolated mouse coronary arteries (CA). To determine the source of superoxide overproduction during H/R we studied CA obtained from transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD) and mice lacking gp91phox using an in vitro vascular ring bioassay. We found that under normoxic conditions CA isolated from wild type (wt) mice, CuZn-SOD Tg mice and gp91phox knock-out mice had similar contractile responses to U46619 and hypoxia and similar dilation responses to acetylcholine. In wt CA, 30 min of hypoxia (1% O2) followed by reoxygenation (16% O2) resulted in further coronary vasoconstriction (internal diameter from 105 ± 11 to 84.5 ± 17.9 μm), whereas this response was completely blocked in both CuZn-SOD Tg and gp91phox knock-out CA (104.3 ± 10.5 to 120.7 ± 14 μm and 143.3 ± 15.3 to 172.7 ± 12.5 μm, respectively, p < 0.01). Furthermore, we show that H/R enhances the generation of superoxide radicals in wt CA (25.8 ± 0.7 relative light units per second (RLU/s)), whereas CuZn-SOD Tg CA (12.2 ± 0.8 RLU/s, p < 0.01) and gp91 phox CA (12.5 ± 0.9 RLU/s, p < 0.01) show reduced levels. These results demonstrate that H/R-induced vasoconstriction is mediated by intracellular superoxide overproduction via endothelial NADPH oxidase gp91 phox. Therefore, increasing endogenous levels of CuZn-SOD in CA may provide a novel cardioprotective strategy for maintaining coronary perfusion under conditions of H/R.

Original languageEnglish (US)
Pages (from-to)24493-24497
Number of pages5
JournalJournal of Biological Chemistry
Issue number23
StatePublished - Jun 4 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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