Important role of superoxide dismutase in EDHF-mediated responses of human mesenteric arteries.
The endothelium synthesizes and releases several vasodilator substances, including prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have identified hydrogen peroxide (H2O2) 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-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.
Morikawa
Keiko
K
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Fujiki
Takako
T
Matoba
Tetsuya
T
Kubota
Hiroshi
H
Hatanaka
Makoto
M
Takahashi
Shosuke
S
Shimokawa
Hiroaki
H
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage; D001685:Biological Factors / Q000494:pharmacology* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000145:classification / Q000502:physiology; D007564:Japan; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012107:Research Design / Q000592:standards; D013482:Superoxide Dismutase / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001562:Benzimidazoles; D001685:Biological Factors; D007527:Isoenzymes; C067410:endothelium-dependent hyperpolarization factor; C086491:NS 1619; D009599:Nitroprusside; D019335:Nitroarginine; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D001920:Bradykinin; D007213:Indomethacin