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(Pro)renin receptor deletion prevents the development of DOCA‐salt hypertension in neuron‐specific (pro)renin receptor knockout mice
Author(s) -
Li Wencehng,
Peng Hua,
Ichihara Atsuhiro,
Feng Yumei
Publication year - 2012
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.26.1_supplement.874.4
Subject(s) - medicine , endocrinology , receptor , knockout mouse , blood pressure , neuron , renin–angiotensin system , chemistry , psychiatry
We previously found the presence of (pro)renin receptor (PRR) in the brain. To elucidate the physiological importance of brain PRR, we developed a neuron‐specific PRR knockout mouse model (Nefh‐PRR). Using real time PCR and immunofluorescence, we observed PRR deletion throughout the brain. Blood pressure (BP) and heart rate (HR) were recorded continuously by telemetry in conscious Nefh‐PRR and control mice (n=5/group) before and during 21 days of deoxycorticosterone acetate‐salt (DOCA, 50mg, 0.9% NaCl drinking solution + tap water) treatment. At baseline, Nefh‐PRR mice exhibited normal BP (mmHg), sympathetic and parasympathetic tone. DOCA‐salt induced hypertension in control mice (137.0±10.5), while Nefh‐PRR mice remained normotensive (114.1±2.9; P<0.05) at the end of experiments. DOCA‐salt significantly increased cardiac (delta HR: −219±6 vs. −66±10 bpm) and vasomotor sympathetic tone (delta BP: −63.7 ± 10.2 vs. −28.7 ± 1.2), and decreased parasympathetic tone (delta HR: 25±7 vs. 147±6 bpm) in control mice. Nefh‐PRR mice exhibited lower sympathetic tone (delta HR: −155±6 bpm; P=0.002, delta BP: − 32.4±5; P=0.05) and higher parasympathetic tone (delta HR: 101±27 bpm; P=0.03) compared to control mice following DOCA‐salt treatment. These data indicate neuron‐specific PRR knockout prevents DOCA‐salt induced hypertension via improvement of autonomic function. (NIH 1P30HL101285, AHA 11SDG7360050)