Premium
Angiotensin (1‐7) Antagonizes the Enhanced Chronotropic Effects of Angiotensin II in Spontaneously Hypertensive Rat (SHR) Brain Neurons
Author(s) -
Modgil Amit,
Zhang Qi,
Yao Fanrong,
O'Rourke Stephen T.,
Sun Chengwen
Publication year - 2010
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.24.1_supplement.lb685
Subject(s) - medicine , endocrinology , pten , chronotropic , angiotensin ii , chemistry , tensin , premovement neuronal activity , hypothalamus , antagonist , receptor , signal transduction , pi3k/akt/mtor pathway , neuroscience , biology , biochemistry , heart rate , blood pressure
Ang (1‐7) plays a major role in counter‐regulating the actions of Ang II in the periphery, but its actions in the CNS are not fully understood. This study was designed to determine the interaction between Ang II and Ang (1‐7) in regulating neuronal activity in neurons cultured from hypothalamus of SHR vs. WKY rats using current clamp recording. Superfusion of neurons with Ang (1‐7) (10 nM‐1 μM) did not alter the neuronal firing rate in either SHR or WKY neurons. Pretreatment of neurons with Ang (1‐7) (100 nM) decreased the Ang II‐induced enhancement in neuronal firing rate in SHR neurons, but not in WKY neurons. This counter‐regulatory action of Ang (1‐7) was blocked by A‐779 (10 μM), a Mas‐receptor antagonist. Previously we demonstrated that the enhanced chronotropic effect of Ang II in SHR neurons is mediated by PI3K. Thus, the role of PTEN (phosphatase and tensin homologue), which dephosphorylates phosphoinositide substrate, was studied in the action of Ang (1‐7). The PTEN inhibitor, BPV (10 μM), abolished the effect of Ang (1‐7) on Ang II action. Incubation of SHR neurons with Ang (1‐7) increased PTEN activity by 116%. The data demonstrate that Ang (1‐7) stimulates PTEN activity via Mas‐R, dephosphorylates phosphatidylinositol‐3,4,5‐trisphosphate, and depresses PI3K signaling pathway, which leads to a counter‐regulatory effect of Ang (1‐7) on Ang II action in neuronal activity of SHR neurons.