Abstract
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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
