TY - JOUR
T1 - Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries
AU - Matoba, Tetsuya
AU - Shimokawa, Hiroaki
AU - Kubota, Hiroshi
AU - Morikawa, Keiko
AU - Fujiki, Takako
AU - Kunihiro, Ikuko
AU - Mukai, Yasushi
AU - Hirakawa, Yoji
AU - Takeshita, Akira
N1 - Funding Information:
We thank Dr. Saku, Dr. Ikejiri, and Ms. Tanaka (Department of Surgery, National Kyushu Medical Center Hospital, Fukuoka, Japan) for cooperation in this study. This work was supported in part by grants (07307010, 10877111, and 12877114) from the Japanese Ministry of Education, Science, Sports, Culture, and Technology, Tokyo, Japan.
PY - 2002
Y1 - 2002
N2 - The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in mice. The present study was designed to examine whether this is also the case in humans. Bradykinin elicited endothelium-dependent relaxations and hyperpolarizations in the presence of indomethacin and Nω-nitro-L-arginine, which thus were attributed to EDHF, in human mesenteric arteries. The EDHF-mediated relaxations were significantly inhibited by catalase, an enzyme that specifically decomposes H2O2, whereas catalase did not affect endothelium-independent hyperpolarizations to levcromakalim. Exogenous H2O2 elicited relaxations and hyperpolarizations in endothelium-stripped arteries. Gap junction inhibitor 18α-glycyrrhetinic acid partially inhibited, whereas inhibitors of cytochrome P450 did not affect the EDHF-mediated relaxations. These results indicate that H2O2 is also a primary EDHF in human mesenteric arteries with some contribution of gap junctions.
AB - The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in mice. The present study was designed to examine whether this is also the case in humans. Bradykinin elicited endothelium-dependent relaxations and hyperpolarizations in the presence of indomethacin and Nω-nitro-L-arginine, which thus were attributed to EDHF, in human mesenteric arteries. The EDHF-mediated relaxations were significantly inhibited by catalase, an enzyme that specifically decomposes H2O2, whereas catalase did not affect endothelium-independent hyperpolarizations to levcromakalim. Exogenous H2O2 elicited relaxations and hyperpolarizations in endothelium-stripped arteries. Gap junction inhibitor 18α-glycyrrhetinic acid partially inhibited, whereas inhibitors of cytochrome P450 did not affect the EDHF-mediated relaxations. These results indicate that H2O2 is also a primary EDHF in human mesenteric arteries with some contribution of gap junctions.
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U2 - 10.1006/bbrc.2001.6278
DO - 10.1006/bbrc.2001.6278
M3 - Article
C2 - 11798159
AN - SCOPUS:0036293354
SN - 0006-291X
VL - 290
SP - 909
EP - 913
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -