Roles of Hypertension in the Rupture of Intracranial Aneurysms

被引:135
作者
Tada, Yoshiteru [1 ,2 ]
Wada, Kosuke [1 ]
Shimada, Kenji [1 ]
Makino, Hiroshi [1 ]
Liang, Elena I. [1 ]
Murakami, Shoko [1 ]
Kudo, Mari [1 ]
Kitazato, Keiko T. [2 ]
Nagahiro, Shinji [2 ]
Hashimoto, Tomoki [1 ]
机构
[1] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94110 USA
[2] Univ Tokushima, Sch Med, Dept Neurosurg, Tokushima 770, Japan
关键词
angiotensins; hypertension; intracranial aneurysm; models; animal; subarachnoid hemorrhage; INDUCED CEREBRAL ANEURYSMS; MOUSE MODEL; MEDICAL PROGRESS; MICE; RISK; ATHEROSCLEROSIS; RECOMMENDATIONS; MANAGEMENT; INCREASES; RENIN;
D O I
10.1161/STROKEAHA.113.003072
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
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页码:579 / 586
页数:8
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