title: Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice.
abstract: 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-α and interleukin-1β in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.
authors.affiliation: 1] Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA [2] Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Hajime
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuwabara
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shikata
authors.affiliation: Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kanematsu
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lawton
authors.affiliation: Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan.
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.affiliation: Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima City, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D017542:Aneurysm, Ruptured / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000803:Angiotensin I / Q000627:therapeutic use*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
chemical_list: C092006:7-Ala-angiotensin (1-7); D057912:Angiotensin II Type 2 Receptor Blockers; D016207:Cytokines; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7)