Important role of superoxide dismutase in EDHF-mediated responses of human mesenteric arteries

Keiko Morikawa, Takako Fujiki, Tetsuya Matoba, Hiroshi Kubota, Makoto Hatanaka, Shosuke Takahashi, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


The endothelium synthesizes and releases several vasodilator substances, including prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have identified hydrogen peroxide (H 2O2) as an EDHF in mouse and human mesenteric arteries and porcine coronary microvessels. We also have recently demonstrated that Cu,Zn-SOD plays an important role in EDHF synthesis in mouse mesenteric arteries. However, it remains to be determined whether SOD also plays an important role in EDHF-mediated responses of human arteries. In this study, we addressed this point in human mesenteric arteries. We used small mesenteric arteries of patients who underwent gastrectomy operations. Isometric tensions and membrane potentials were recorded in the presence of indomethacin and N ω-nitro-L-arginine to inhibit the synthesis of prostacyclin and NO, respectively. Pretreatment with Tiron, a cell-permeable SOD-mimetic, significantly enhanced the EDHF-mediated relaxations and hyperpolarizations to bradykinin, and this effect was abolished by catalase, indicating that this enhancing effect was achieved by H2O2. By contrast, Tiron did not affect endothelium-independent relaxations, indicating that the enhancing effect of Tiron is not caused by the enhancement of vascular smooth muscle responses. These results indicate that SOD plays an important role in EDHF-mediated relaxations and hyperpolarizations of human mesenteric arteries.

Original languageEnglish
Pages (from-to)552-556
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Issue number5
Publication statusPublished - Nov 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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