{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T19:28:36Z","timestamp":1779218916851,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T00:00:00Z","timestamp":1400544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>An angiotensin 2 type 1 receptor blocker, olmesartan, and a calcium channel blocker, azelnidipine, possess not only an antihypertensive effect but also an antioxidative effect and other beneficial effects. In the present study, we examined the efficacy of olmesartan and azelnidipine monotherapy (2 mg\/kg or 10 mg\/kg each) and their combination therapy (1 mg\/kg each) on stroke\u2010prone spontaneously hypertensive rats (SHR\u2010SP) in relation to oxidative stress, inflammation, and the neurovascular unit. In comparison with the vehicle group, body weight, regional cerebral blood flow, and motor function were preserved, whereas systolic blood pressure and diastolic blood pressure decreased in the five drug\u2010treatment groups. Spontaneous infarct volume decreased with the low\u2010dose combination of olmesartan plus azelnidipine and with the high\u2010dose olmesartan, with a further decrease in the high\u2010dose azelnidipine group. In addition, these drugs dose\u2010dependently reduced oxidative stresses, proinflammatory molecules, and well\u2010preserved components of the neurovascular unit. The low\u2010dose combination of olmesartan plus azelnidipine showed a better effect than the low\u2010dose olmesartan or azelnidipine monotherapy. The present study shows that the low\u2010dose combination of olmesartan plus azelnidipine demonstrates a greater synergistic benefit than monotherapy with a low\u2010dose of olmesartan or azelnidipine in SHR\u2010SP for preventing spontaneous infarct volume, reducing oxidative stresses and proinflammatory molecules, and imparting neurovascular protection. In addition, a high\u2010dose of olmesartan showed a greater benefit without the lowering of blood pressure, probably because of the antioxidative and anti\u2010inflammatory effects. A high dose of azelnidipine showed the best benefit, probably because of the two effects mentioned above related to the lowering of blood pressure. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23406","type":"journal-article","created":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T05:23:24Z","timestamp":1400563404000},"page":"1330-1337","source":"Crossref","is-referenced-by-count":9,"title":["Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke\u2010prone spontaneously hypertensive rats"],"prefix":"10.1002","volume":"92","author":[{"given":"Yoshio","family":"Omote","sequence":"first","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syoichiro","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Kurata","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Hishikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Shikatacho Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,20]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"339","article-title":"Ovarian angiogenesis. Phenotypic characterization of endothelial cells in a physiological model of blood vessel growth and regression","volume":"147","author":"Augustin HG","year":"1995","journal-title":"Am J Pathol"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.8.1671"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-11-66"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1479164112447310"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164104225016074"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.03.054"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.108894"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.10.046"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2013.02.073"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.07.038"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2007.05.007"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.228.305"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.12.010"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21747"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2010.241"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082082"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.02.020"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641963.2012.666603"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-007-0481-8"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.23406","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.23406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T10:35:13Z","timestamp":1696502113000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.23406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,20]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1002\/jnr.23406"],"URL":"https:\/\/doi.org\/10.1002\/jnr.23406","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,20]]}}}