Abstract 13442: Renin-Angiotensin Metabolite Profiling via LC-MS/MS Reveals Sex Dependent Differences Induced by High-Salt Diet in Dahl-S Rats

Background: Understanding how sex influences the pathophysiology of cardiovascular and renal disease may enhance precision medicine approaches that account for sex specific biologic differences in these diseases. Nevertheless, characterization of preclinical models often fail to account for the role of sex on important pathophysiologic mechanisms. The renin-angiotensin-aldosterone system (RAAS) plays a central role in the development and progression of cardiovascular and renal disease. In addition to the classic RAAS pathway, an alternative RAAS pathway produces angiotensins (e.g. Ang [1-7]) that can counteract classical RAAS hormones such as Angiotensin (Ang) II. We hypothesized that RAAS profiling in a high-salt fed Dahl-S rat model would reveal significant sex differences in both classic and alternative RAAS pathways. Methods/Results: Ten week-old male and female Dahl-S rats were fed either 0.2% salt normal chow (SS-NC), or 8% high-salt diet (SS-HS) for eight weeks (n=6-8/group). Equilibrium RAAS profiling via LC-MS/MS was performed in lithium heparin plasma samples. In response to high-salt diet, both male and female SS-HS rats had significant (p Conclusion: High-salt diet induces significant sex-dependent differences in both classic and alternative RAAS pathways of Dahl-S rats and may provide important insight into the sex-dependent differences of cardiovascular and renal injury seen in this model.