期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 35, 期 7, 页码 1163-1168出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2015.30
关键词
inflammation; Intracranial aneurysm; stroke; subarachnoid hemorrhage
资金
- National Institute of Neurological Disorders and Stroke (NIH/NINDS) [R01NS055876, R01NS082280]
- Brain Aneurysm Foundation Shirley Dudek Demmer Chair of Research
- Grants-in-Aid for Scientific Research [15K10306, 15H04950] Funding Source: KAKEN
Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-a and interleukin-1 beta in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.
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