Roles of hypertension in the rupture of intracranial aneurysms
BACKGROUND AND PURPOSE: 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.
angiotensins, hypertension, intracranial aneurysm, models, animal, subarachnoid hemorrhage
Medical Subject Headings
Aneurysm, Ruptured (chemically induced, complications); Animals; Antihypertensive Agents (therapeutic use); Blood Pressure (physiology); Captopril (therapeutic use); Desoxycorticosterone Acetate; Dose-Response Relationship, Drug; Hydralazine (therapeutic use); Hypertension (chemically induced, complications); Intracranial Aneurysm (chemically induced, complications); Losartan (therapeutic use); Male; Mice; Mice, Inbred C57BL; Pancreatic Elastase; Renin-Angiotensin System (drug effects); Risk Factors; Subarachnoid Hemorrhage (complications); Survival Analysis; Treatment Outcome
Digital Object Identifier (DOI)
Tada, Yoshiteru; Wada, Kosuke; Shimada, Kenji; Makino, Hiroshi; Liang, Elena I.; Murakami, Shoko; Kudo, Mari; Kitazato, Keiko T.; Nagahiro, Shinji; and Hashimoto, Tomoki, "Roles of hypertension in the rupture of intracranial aneurysms" (2014). Translational Neuroscience. 1698.