LAUSR

There have been many hypertension mouse models created by transgenesis. The transgenesis technologies to create hypertensive mouse models mostly target the renin-angiotensin system (RAS). Here, we show that enhanced expression of neprilysin driven by the myeloid-specific c-fms promoter causes systemic hypertension in mice. [Method] Transgenic mice, termed Nep mice, were created with a construct containing the c-fms promoter and the neprilysin gene (MME). Blood pressure was measured by tail-cuff. Circulating vasoactive substances were analyzed by ELISAs. [Results] Nep mice showed higher systolic blood pressure compared with WT mice (117.0±1.75 vs. 107.1±2.373 mmHg, p=0.0018). The sodium concentration in a 24hr urine was significantly lower in Nep mice (0.2093±0.0039 vs. 0.2445±0.0054 μmol/μl urine, p=0.0004). The concentration of circulating neprilysin was significantly higher in Nep mice (3085±750.5 vs. 1098±197.1 pg/ml, p=0.0283). Notably, the plasma concentration of ANP showed no significant difference between Nep and WT mice although hypertension usually causes an ANP increase. [Conclusion] Overexpression of neprilysin in monocytes causes systemic hypertension associated with sodium and water retention. These mice might be useful for studying the pathologies of heart diseases and hypertension due to volume overload, and in addition, other neprilysin related diseases like Alzheimer’s disease to investigate the interaction with immune cells and beta-amyloid which is cleaved by neprilysin. NIH R01 AI164519 (KEB, P.I.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.