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Angiotensin‐(1‐7) inhibits angiotensin II intra‐neuronal signaling
Author(s) -
Yang RuiFang,
Yin JingXiang,
Li YuLong,
Schultz Harold D.,
Zimmerman Matthew C.
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.1051.12
Subject(s) - angiotensin ii , endocrinology , medicine , nitric oxide , renin–angiotensin system , chemistry , antagonist , receptor , pharmacology , blood pressure
Elevated levels of superoxide (O 2 •− ) induced by angiotensin II (AngII) play a vital role in the sympathoexcitation associated with many neuro‐cardiovascular diseases, such as hypertension and heart failure. Recent studies report that angiotensin‐(1‐7) [Ang‐(1‐7)] increases neuronal levels of nitric oxide (NO • ), which can rapidly react with O 2 •− to limit its potential signaling. We hypothesized that Ang‐(1‐7) inhibits AngII intra‐neuronal signaling by modulating O 2 •− levels. Using differentiated CATH.a neurons, we observed that the AngII (100 nM)‐induced increase in O 2 •− , as measured by EPR spectroscopy and DHE fluorescence, was markedly attenuated by pretreatment with 100 nM Ang‐(1‐7) (EPR arbitrary units/10 3 neurons: vehicle = 938 ± 67; AngII = 1310 ± 92*; Ang‐(1‐7) + AngII = 1004 ± 95; *P<0.05 vs. vehicle and Ang‐(1‐7) + AngII). This inhibition was blocked by the Ang‐(1‐7) receptor antagonist A‐779 (1261 ± 107; P<0.05 vs. Ang‐(1‐7) + AngII). Further, AngII‐induced inhibition of neuronal K + current (I Kv ; 49 ± 9% inhibition) was attenuated by Ang‐(1‐7) (22 ± 4% inhibition; P<0.05 vs. AngII alone). These findings indicate that Ang‐(1‐7) attenuates the AngII‐induced increase in O 2 •− and inhibition of I Kv . Ang‐(1‐7) signaling in neurons may play an important protective role counterbalancing AngII sympathoexcitation in the pathogenesis of cardiovascular diseases. NIH P20RR017675 and P01HL062222