{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:17:00Z","timestamp":1791296220391,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Systemic hypertension has long been considered a risk factor of aneurysmal rupture. However, a causal link between systemic hypertension and the development of aneurysmal rupture has not been established. In this study, using a mouse model of intracranial aneurysm rupture, we examined the roles of systemic hypertension in the development of aneurysmal rupture.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Aneurysms were induced by a combination of deoxycorticosterone acetate (DOCA)-salt and a single injection of elastase into the cerebrospinal fluid in mice. Antihypertensive treatment was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. Hydralazine (direct vasodilator) or discontinuation of DOCA-salt treatment was used to assess the roles of systemic hypertension. Captopril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin II type 1 receptor antagonist) was used to assess the roles of the local renin\u2013angiotensin system in the vascular wall.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Normalization of blood pressure by hydralazine significantly reduced the incidence of ruptured aneurysms and the rupture rate. There was a dose-dependent relationship between reduction of blood pressure and prevention of aneurysmal rupture. Captopril and losartan were able to reduce rupture rate without affecting systemic hypertension induced by DOCA-salt treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin\u2013angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.113.003072","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T02:54:05Z","timestamp":1388112845000},"page":"579-586","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":158,"title":["Roles of Hypertension in the Rupture of Intracranial Aneurysms"],"prefix":"10.1161","volume":"45","author":[{"given":"Yoshiteru","family":"Tada","sequence":"first","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Wada","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Shimada","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Makino","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Liang","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Murakami","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Kudo","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); and Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan (Y.T., K.T.K, S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko T.","family":"Kitazato","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA (Y.T., K.W., K.S., H.M., E.I.L., S.M., M.K., T.H.); 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