Roles of endothelial oxidases in endothelium-derived hyperpolarizing factor responses in mice

Aya Takaki, Keiko Morikawa, Yoshinori Murayama, Hiroto Yamagishi, Maki Hosoya, Junko Ohashi, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

The endothelium synthesizes and releases several vasodilator substances, including prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans and that superoxide anions derived from endothelial nitric oxide synthases (NOSs) system are an important precursor for EDHF/H2O2 in mice. There are several intracellular sources of superoxide anions other than NOSs, including NAD(P)H oxidase, xanthine oxidase, lipoxygenase, and mitochondrial electron transport chain. In this study, we examined the possible role of endothelial oxidases other than NOSs in the EDHF-mediated responses. In angiotensin II-infused mice, both EDHF-mediated relaxations and hyperpolarizations to acetylcholine were significantly reduced, nitric oxide-mediated relaxations were rather enhanced, and vascular smooth muscle responses were preserved. Antihypertensive treatment normalized blood pressure but failed to improve EDHF-mediated responses in those mice. Acute inhibition of endothelial oxidases other than NOSs, including NAD(P)H oxidase, xanthine oxidase, lipoxygenase, or mitochondrial electron transport chain, had no inhibitory effects on EDHF-mediated responses. Furthermore, in p47phox-knockout mice, EDHF-mediated responses were unaltered. These results suggest that endothelial oxidases other than NOSs are not involved in EDHF/H2O2 responses in mice, suggesting a specific link between endothelial NOSs system and EDHF responses under physiological conditions.

Original languageEnglish
Pages (from-to)510-517
Number of pages8
JournalJournal of cardiovascular pharmacology
Volume52
Issue number6
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Hydrogen peroxide
  • Lipoxygenase
  • Membrane potential
  • Mitochondrial electron transport chain
  • NAD(P)H oxidase
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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