Premium
Mas mediated cerebroprotective action of the angiotensin type 2 receptor agonist Compound 21 in ischemic stroke.
Author(s) -
Patel Neal Anil,
Joseph Jason,
Pioquinto David,
Ludin Jacob,
Greenstein David,
Sumners Colin,
Steckelings Ulrike Muscha
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.693.6
Subject(s) - agonist , angiotensin ii , receptor , antagonist , medicine , pharmacology , receptor antagonist , anesthesia , stroke (engine) , endothelin receptor , blockade , endocrinology , mechanical engineering , engineering
Recent studies indicate that angiotensin‐(1–7) [Ang‐(1–7)] or the angiotensin type 2 receptor (AT2R) agonist Compound 21 (C21) exert significant cerebroprotective actions against ischemic stroke. Based on recent evidence of dimerization between AT2R and the Ang‐(1–7) receptor Mas, we tested whether the Mas antagonist A‐779 can alter the cerebroprotective actions of C21 against ischemic stroke produced by endothelin‐1 (ET‐1) induced middle cerebral artery occlusion (MCAO). Adult male Sprague Dawley (SD) rats were pre‐treated with A‐779 (0.0075ug/h) or artificial cerebrospinal fluid (aCSF) via intracerebroventricular (ICV) infusion for 7 days prior to ET‐1 induced MCAO. IP administration of C21 (0.03 mg/kg) at 4 and 12 hours post‐MCAO significantly reduced the cerebral infarct size of ipsilateral gray matter, and attenuated the associated neurological deficits when compared with rats that had received IP 0.9% saline at the same time points. ICV infusion of A‐779 abolished the treatment effect of C21 on infarct size and neurological deficits, measured 72 h after MCAO induction (n=13–16), but alone had no significant effects on infarct size or behavioral scores. These data suggest that the cerebroprotective action of C21 either involves activation of Mas or that due to AT2R‐Mas‐heterodimerzation, blockade of the receptor Mas also prevents signaling of the AT2R.