[BP.08.06] AT2 RECEPTOR-INTERACTING PROTEIN ATTENUATES ISCHEMIC BRAIN DAMAGE IN CONCERT WITH AT2 RECEPTOR ACTIVATION. (September 2017)

• Record Type: Journal Article
• Authors: Iwanami, J.; Mogi, M.; Wang, X.; Tsukuda, K.; Higaki, A.; Kukida, M.; Nakaoka, H.; Yamauchi, T.; Bai, H.; Shan, B.; Min, L.; Horiuchi, M.
• Is Part Of: Journal of hypertension. Volume 35(2017)Supplement 2
• Publication Date: 2017-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000523779.63113.f4
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Accumulating evidences and previous our research suggest that angiotensin II type 2 (AT2) receptor stimulation could contribute to protection against ischemic brain damage. We have cloned ATIP (AT2 receptor interacting protein) as a protein interacting specifically with the C-terminal tail of the AT2 receptor, and suggest that ATIP might play key roles in diverse mechanisms of AT2 receptor signaling. However, the effect of ATIP on ischemic brain damage is unclear. Therefore, we investigated the effects of the ATIP and compound 21 (C21), a selective non-peptidic AT2 receptor agonist, on focal cerebral ischemia. Design and method: Ten-week-old male ATIP-transgenic (ATIP-Tg) and littermate (WT) mice were subjected to middle cerebral artery (MCA) occlusion with silicon-coated micro-filament. C21 (10 μg/kg/day) was administered 2 weeks before MCA occlusion. Twenty-four hours after MCA occlusion, neurological deficit and ischemic area were examined. Cerebral blood flow (CBF) before and after MCA occlusion were measured by laser speckle flowmetry. Expression of mRNA was determined by real-time RT-PCR. Collateral circulation was evaluated by the perfusion of India ink. Results: Systolic blood pressure did not differ between WT and ATIP-Tg mice. There were no significant differences in neurological deficit and ischemic size without C21 treatment between WT and ATIP-Tg mice. Treatment with C21 improved neurological deficit and decreased ischemic size in both strains, whereas these protective effects of C21 were more marked in ATIP-Tg mice compared with WT mice. Expression of methyl methanesulfonate sensitive 2 (MMS2) mRNA as a neuroprotective factor increased in ipsilateral hemisphere of ATIP-Tg mice compared with contralateral hemisphere. Treatment with C21 did not influence CBF in the core region of ischemic area after MCA occlusion in both strains; however, the reduction of CBF in penumbra region after MCA occlusion was attenuated in ATIP-Tg mice with C21 administration. Moreover, we observed that treatment with C21 tended to increase the cerebral collateral number before MCA occlusion in ATIP-Tg mice. Conclusions: These results suggested that ATIP could enhance the cerebral protective effects of AT2 receptor stimulation at least in part due to the increase of CBF and MMS2 expression.