Cerebroprotective action of angiotensin 1‐7 in a rat model of ischemic stroke

Abstract

Recent progress in cardiovascular therapy suggests that stimulation of Angiotensin Converting Enzyme 2 (ACE2), production of Angiotensin 1‐7 (Ang 1‐7), and activation of the Ang 1‐7 receptor, Mas, are viable targets for disease prevention and treatment. We proposed that central administration of Ang 1‐7 via lateral ventricular cannula will provide cerebroprotection in a rat model of Endothelin‐1 (ET‐1)‐induced middle cerebral artery occlusion (MCAO). Prior to ET‐1 induced MCAO, rats were treated with intracerebroventricular Ang 1‐7 (1µg/h) or artificial Cerebrospinal Fluid (aCSF) for 5 days. Ang 1‐7 treatment reduced neurological deficits and infarct size measured 72 h after MCAO induction. Infarct size was reduced to 15.23 ± 5.77% (n = 9) of ipsilateral gray matter in the Ang 1‐7 treated rats compared with 36.94 ± 7.56% (n = 12) in artificial Cerebrospinal Fluid (aCSF) controls. Neurological deficits were also reduced in Ang 1‐7 treated rats as indicated by a lower Benderson Exam Score of 0.22 ± 0.15 (n = 9) compared to 1.08 ± 0.31 (n = 12) in control rats, a higher Garcia Exam Score of 17.56 ± 0.18 (n = 9) compared to 14.00 ± 1.10 (n = 12) in control rats, and improved sunflower seed eating from 146 ± 23 s and 14 ± 1 (n = 9) shell pieces compared to 293 ± 7 s and 29 ± 1 shell pieces (n = 12) in control rats. This provides the first demonstration of the cerebroprotective properties of Ang 1‐7 during ischemic stroke.