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Human prorenin induces Ang II‐independent pressor response in neuron‐specific human (pro)renin receptor transgenic mice
Author(s) -
Peng Hua,
Li Wenchen,
Sigmund Curt D,
Feng Yumei
Publication year - 2013
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.27.1_supplement.1165.13
Subject(s) - losartan , endocrinology , medicine , renin–angiotensin system , chemistry , nadph oxidase , receptor , angiotensin ii , genetically modified mouse , transgene , blood pressure , biology , oxidative stress , biochemistry , gene
We previously showed that (pro)renin receptor (PRR) mediated Ang II‐independent signals in neuronal cells. To elucidate the significance of these signaling pathways in vivo, we developed a novel neuron‐specific human PRR transgenic mouse model (syn‐hPRR). Despite high hPRR expression level selectively in brain of syn‐hPRR mice, baseline blood pressure (BP, mmHg) and heart rate (HR, bpm) were similar in syn‐hPRR and NT mice measured by telemetry (n=8/group). However, the cardiac (ÄHR: −68.4±1.3 VS. −45.3±1.4) and vasomotor (ÄMAP: −41.1±2.1 VS. −28.9±0.4) sympathetic tones were significantly higher in syn‐hPRR compared with NT mice. Interestingly, ICV infusion (0.3μl/min) of human prorenin (300ng) significantly increased BP in syn‐hPRR mice (ÄMAP: 22.5±4.6, P<0.05), but not in NT mice (ÄMAP: 1.6±0.8). Although human prorenin‐induced pressor response in syn‐hPRR mice could not be blocked by ICV infusion of losartan (30μg/μl) or captopril (10μg/μl), the pressor response was abolished by ICV infusion of either reactive oxygen species (ROS) scavenger tempol (100μM, ÄMAP: 4.5±0.5 P<0.05) or NADPH oxidase inhibitor diphenyleneiodonium (10μM, ÄMAP: 4.7±1.0 P<0.05). These data suggest that human prorenin via binding to hPRR mediates Ang II‐independent pressor response in syn‐hPRR mice through increase in brain ROS levels, suggesting a novel role of Ang II‐independent pathways of human PRR in hypertension.