title: Angiotensin-(1-7) modulates renin-angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats.
abstract: Angiotensin-(1-7) [Ang-(1-7)] has beneficial effects against hypertension-induced damage in heart and kidney, but its effects in brain are not clear as yet. The present study aimed to investigate the protective effects of Ang-(1-7) on the physiopathologic changes caused by hypertension in brain of spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats received intracerebroventricular (I.C.V.) infusion of artificial cerebrospinal fluid (aCSF) while SHRs received I.C.V. infusion of Ang-(1-7), Mas receptor antagonist A-779 and aCSF for 4 weeks. Brain tissues were collected and analyzed by western blot, enzyme immunoassay, spectrophotometric assays and terminal deoxynucleotidyl transferase-mediated dUTP end-labeling (TUNEL) staining. Our study showed that infusion of Ang-(1-7) for 4 weeks significantly reduced the expression of Angiotensin II and Angiotensin II type 1 receptors in SHR brain. Additionally, it decreased the levels of malondialdehyde and elevated total superoxide dismutase activity, which was accompanied by reductions of NADPH oxidase subunit gp91(phox) and inducible nitric oxide synthase in the brain of SHR. The increases of the percentage of TUNEL-positive neurons and Bax to Bcl-2 ratio in SHR brain were also attenuated by Ang-(1-7). The anti-oxidative and anti-apoptosis effects of Ang-(1-7) are independent of blood pressure reduction and can be partially abolished by A-779. These findings suggest that chronic treatment with Ang-(1-7) is beneficial to attenuate hypertension-induced physiopathologic changes in brain and may be helpful to prevent hypertension-related cerebrovascular diseases.
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Jianquan
authors.initials: J
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D008315:Malondialdehyde; D000803:Angiotensin I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; C118790:angiotensin I (1-7)