title: Roles of hypertension in the rupture of intracranial aneurysms.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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-angiotensin system in the vascular wall.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin-angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.
authors.affiliation: 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.).
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Tada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Wada
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Makino
authors.forename: Elena I
authors.initials: EI
authors.lastname: Liang
authors.forename: Shoko
authors.initials: S
authors.lastname: Murakami
authors.forename: Mari
authors.initials: M
authors.lastname: Kudo
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.forename: Tomoki
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D017542:Aneurysm, Ruptured / Q000139:chemically induced / Q000150:complications*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D002216:Captopril / Q000627:therapeutic use; D064791:Desoxycorticosterone Acetate; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000150:complications*; D002532:Intracranial Aneurysm / Q000139:chemically induced / Q000150:complications*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000150:complications; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D006830:Hydralazine; D064791:Desoxycorticosterone Acetate; D002216:Captopril; D010196:Pancreatic Elastase; D019808:Losartan
keywords: angiotensins; hypertension; intracranial aneurysm; models, animal; subarachnoid hemorrhage