Endothelium-derived hydrogen peroxide accounts for the enhancing effect of an angiotensin-converting enzyme inhibitor on endothelium-derived hyperpolarizing factor-mediated responses in mice

Takako Fujiki, Hiroaki Shimokawa, Keiko Morikawa, Hiroshi Kubota, Makoto Hatanaka, M. A.Hassan Talukder, Tetsuya Matoba, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Background - We have recently identified that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans, for which endothelial nitric oxide synthase (eNOS) is an important source. Angiotensin-converting enzyme (ACE) inhibitors are known to enhance EDHF-mediated responses. In this study, we examined whether endothelium-derived H2O2 accounts for the enhancing effect of an ACE inhibitor on EDHF-mediated responses and, if so, what mechanism is involved. Methods and Results - Control and eNOS-/- mice were maintained with or without temocapril (10 mg/kg per day orally) for 4 weeks, and isometric tensions and membrane potentials of mesenteric arteries were recorded. In control mice, temocapril treatment significantly enhanced EDHF-mediated relaxations and hyperpolarizations to acetylcholine (n=8 each). Catalase, a specific scavenger of H2O2, abolished the beneficial effects of temocapril, although it did not affect endothelium-independent relaxations to sodium nitroprusside or NS1619, a direct opener of KCa channels (n=6 each). Western blot analysis demonstrated that the temocapril treatment significantly upregulated the expression of eNOS. By contrast, this enhancing effect of temocapril was absent in eNOS -/- mice (n=6). Conclusions - These results indicate that endothelium-derived H2O2 accounts for the enhancing effect of temocapril on EDHF-mediated responses caused in part by eNOS upregulation, further supporting our H2O2 theory.

Original languageEnglish
Pages (from-to)766-771
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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