2001 Fiscal Year Final Research Report Summary
A study forthe effects of estrogen on actions ofendothelium-derived hyperpolarizing factor
| Project/Area Number |
11470342
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SAKUMA Ichiro Hokkaido Univ., Hospital, Lec., 医学部・附属病院, 講師 (40260393)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Seiichiro Hokkaido Univ. Grad. Sch. of Med., Prof., 大学院・医学研究科, 教授 (60001898)
FUKAO Mitsuhiro Hokkaido Univ. Grad. Sch. of Med., Assist. Prof., 大学院・医学研究科, 助手 (10250432)
TOHSE Noritsugu Sapporo Med. Univ. Sch. of Med., Pro., 医学部, 教授 (80192657)
MAKITA Naomasa Hokkaido Univ. Grad. Sch. of Med., Assist. Prof., 大学院・医学研究科, 助手 (00312356)
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| Project Period (FY) |
1999 – 2001
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| Keywords | endothelium-derived hyperpolarizing factor / potassium channel / rat / mesenteric artery / resting membrane potential / estrogen / ovariectomy / connexin |
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| Research Abstract |
Endothelium-derived hyperpolarizing factor (EDHF) is released from endothelial cells and function to open reseitance vessels and have a pivotal role in the regulation of blood pressure and microcirculalion of organs.There are some candidates for EDHF, such as P450 metabolite, H_2O_2 and pottasium ion, and one of EDHFs is now thought to be electrical transmission of hypeipolarization of the endothelial cell membrane through gap junction. Estrogen is cardio- and vessel-protective and contributes to help women free from atherosclerosis and ischemic heart disease. The protective actions may arise, in part, from its effect on EDHF. Since gap junction consists of connexins and they are dramatically modulated by estrogen, we tried to investigate the nature of EDHF using estrogen as a clue. Middle-aged female rats was ovariectomized (OVX) or then estrogen-replaced (ERT), and compared with sham-operated ones (CON). The resting membrane potential of the endothelium-intact mesenteric artery of OVX was shallower than that of CON, and reversed in ERT. Acetylcholine-induced hypeipolarization and relaxation of the mesenteric artery were impaired in OVX and recovered in ERT. Immunostaining of connexin 43 using specific antibody revealed a confound decrease in connexin in OVX compared with CON and ERT. Western blotting of connexin 43 protein showed a decrease in the protein expression in OVX compared with the others. To further investigate the nature of EDHF we checked the presence of mRNAs of K channels and now started seeking the role of these channels in EDHF function.
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