Roles of Hypertension in the Rupture of Intracranial Aneurysms

Abstract

Background and Purpose Systemic hypertension has long been considered as 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 induced hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Anti-hypertensive treatment was started six 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 the discontinuation of the 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 the reduction of blood pressure and the prevention of aneurysmal rupture. Captopril and losartan were able to reduce the rupture rates 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.

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

“…16,24 More importantly, human intracranial aneurysms and aneurysms in this model share the common end phenotype, i.e., aneurysmal rupture and associated symptoms. 13,14 This model with or without modifications have been successfully used by other groups to study the mechanisms for aneurysmal formation and rupture. 3,28 Clinical studies that assess the correlation between aneurysmal rupture and the use of agents that affect the Ang-(1-7) system will be need to validate our findings.…”

“…Using the tail cuff method, systolic blood pressure was measured in the mice before aneurysm induction and every week after the elastase injection. 13,14 Real-Time PCR Analysis…”

“…We used a mouse model of intracranial aneurysms in which spontaneous aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) causes neurologic symptoms. 13,14 …”

Primary Cesarean Delivery Complicated by the Incidental Finding of a Cerebral Aneurysm: Selecting a Safe Anesthesia Technique

“…Particularly, the role of systemic blood pressure was shown to be important in rupturing the aneurysm. In an animal study reduction of blood pressure with hydralazine correlated well with prevention of aneurysm rupture [3] . Other risk factors are history of previous aneurysm rupture and a blunt head trauma with subsequent development of cerebral aneurysms [4,5] .…”

Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

“…7,9 The mice also received a single injection of elastase solution (35 milli-units Elastase: E7885, Sigma Aldrich dissolved in 2.5 μL of phosphate-buffered saline) into the cerebrospinal fluid in the right basal cistern on the same day as the DOCA pellet implantation. [6][7][8] The nephrectomy was performed under general anesthesia with 2% isoflurane. The elastase injection was performed under general anesthesia induced by an intraperitoneal injection of ketamine (100 mg/kg) and xylazine (10 mg/kg).…”