Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice

Kenji Shimada, Hajime Furukawa, Kosuke Wada, Yuan Wei, Yoshiteru Tada, Atsushi Kuwabara, Fumiaki Shikata, Yasuhisa Kanematsu, Michael T. Lawton, Keiko T. Kitazato, Shinji Nagahiro, Tomoki Hashimoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1163-1168
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

Keywords

  • Intracranial aneurysm
  • inflammation
  • stroke
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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