@article{oai:kumadai.repo.nii.ac.jp:00026689,
 author = {名幸, 久仁 and 片岡, 恵一郎 and 鯉渕, 信孝 and 董, 一飛 and 外山, 研介 and 山本, 英一郎 and 安田, 修 and 一條, 秀憲 and Ogawa, Hisao and 小川, 久雄 and 光山, 勝慶 and Nako, Hisato and 片岡, 恵一郎 and Kataoka, Keiichiro and Koibuchi, Nobutaka and Dong, Yi-Fei and Toyama, Kensuke and 山本, 英一郎 and Yamamoto, Eiichiro and Yasuda, Osamu and Ichijo, Hidenori and Ogawa, Hisao and 小川, 久雄 and 光山, 勝慶 and Kim-Mitsuyama, Shokei},
 issue = {2},
 journal = {Hypertension Research},
 month = {Feb},
 note = {application/pdf, application/pdf, 論文(Article), This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress-induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury., http://www.nature.com/hr/journal/v35/n2/abs/hr2011175a.html},
 pages = {194--200},
 title = {Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: The critical role of ASK1 and VEGF},
 volume = {35},
 year = {2012},
 yomi = {オガワ, ヒサオ and カタオカ, ケイイチロウ and ヤマモト, エイイチロウ and オガワ, ヒサオ and ミツヤマ, ショウケイ}
}