title: The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7) in the nucleus tractus solitarii of rats.
abstract: Angiotensin-1-7 [Ang-(1-7)], acting via the Mas receptor in the central nervous system, is involved in the regulation of cardiovascular activity. Nitric oxide (NO) is implicated as an important modulator in the nucleus tractus solitarii (NTS), a key region involved in control of cardiovascular activity. The aim of the present study was to determine the role of phosphatidylinositol 3-kinase (PI3K) signaling in mediating the effect of Ang-(1-7) on NO generation in the NTS. In Sprague-Dawley rats, acute injection of Ang-(1-7) into the NTS significantly increased NO generation and neuronal/endothelial NO synthase (n/eNOS) activity, which were abolished by the selective Mas receptor antagonist d-Alanine-[Ang-(1-7)] (A-779), the PI3K inhibitor LY294002, or the Akt inhibitor triciribine (TCN). Western blotting analysis further demonstrated that Ang-(1-7) significantly increased levels of Akt/NOS phosphorylation in the NTS, and Ang-(1-7)-induced e/nNOS phosphorylation was antagonized by LY294002 or TCN. Furthermore, gene knockdown of PI3K by lentivirus containing small hairpin RNA in the NTS prevented the Ang-(1-7)-induced increases in NOS/Akt phosphorylation and NO production. The physiological (in vivo) experiments showed that pretreatment with the NOS inhibitor l-NAME, LY294002, or TCN abolished the decreases in blood pressure, heart rate, and renal sympathetic nerve activity induced by Ang-(1-7) injected into the NTS. Our findings suggest that nitric oxide release meditated by the Mas-PI3K-NOS signaling pathway is involved in the cardiovascular effects of Ang-(1-7) in the NTS.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhao-Tang
authors.initials: ZT
authors.lastname: Wu
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chang-Zhen
authors.initials: CZ
authors.lastname: Ren
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ru-Wen
authors.initials: RW
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jia-Cen
authors.initials: JC
authors.lastname: Sun
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yang-Kai
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China. Electronic address: dfsu2008@gmail.com.
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, China. Electronic address: wangwz68@163.com.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D009569:Nitric Oxide; D000803:Angiotensin I; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; C118790:angiotensin I (1-7)
keywords: Angiotensin-1-7; Nitric oxide; Nucleus tractus solitarii; PI3K signaling; shRNA