Female sex in a mouse model of salt-sensitive hypertension was associated with greater increases in blood pressure and significant reductions in glomerular filtration rate compared to males (p<0.05).
This preclinical study demonstrates that blood pressure, GFR, immune cell infiltration, and renal endothelial cell processing and presentation pathways are regulated in a sex-dependent manner in salt-sensitive hypertension.
p-value: p=<0.05
Evidence indicates that salt-sensitive hypertension (SSHTN) differs pathophysiologically by sex, with females showing increased risk of salt sensitivity and larger increases in blood pressure (BP) relative to males. Importantly, inflammation and endothelial dysfunction are known contributors to elevated BP in salt sensitivity. Our previous data show that renal endothelial cells (RECs) regulate immunological synapse–related proteins, including major histocompatibility complex I and II (MHC I/II), in a sex-dependent manner, potentially driving end-organ inflammation. We propose that sex-specific mechanisms in REC antigen processing and presentation contribute to the differential pathophysiology and inflammatory responses observed between males and females in SSHTN. Male and female C57Bl/6J mice underwent the N(G)-Nitro-L-arginine-methyl ester (LN) / high salt diet (HS) (4.0%) protocol of SSHTN. We measured 24-hour conscious BPs by radiotelemetry and conscious glomerular filtration rates (GFRs). Blood, urine, and organs were harvested for REC RNA sequencing, flow cytometry, and molecular analysis. Mean blood pressure was consistently elevated from baseline in both sexes, especially in females (p< 0.05). GFR remained unchanged in male mice, however there was a significant reduction in GFR in female LN-HS mice (p< 0.05). Urine sodium excretion was unchanged between the sexes on the LN-HS protocol. Plasma soluble vascular cell adhesion molecule-1 was increased in male mice relative to female (p< 0.05). There was no change between the sexes in gene or protein expression of MHCI/II in whole kidney, however male kidneys demonstrated an increase in TAP1 protein expression (p< 0.05) relative to females. Flow cytometry of immune cell populations in whole kidney revealed that LN-HS males have decreased CD8+ T Cells (p< 0.05), a trending increase in CD4+ T Cells (p< 0.1), and a decrease in MHCII+ antigen presenting cells (p< 0.05) relative to LN-HS females. RNA sequencing of RECs from LN-HS mice shows profound sex-dependent upregulation of antigen processing (padj< 0.05), presentation (padj< 0.05), and adhesion genes (padj< 0.05). Analysis of antigen processing and presentation protein expression in RECs isolated from SSHTN mice is ongoing. Future mechanistic studies include a reductionist in vitro model of SSHTN utilizing isolated RECs from donated human kidneys. Overall, we demonstrate that BP, GFR, immune cell infiltration, and REC processing and presentation pathways are regulated in a sex-dependent manner in SSHTN. Our results suggest a need for novel therapeutic strategies to differentially target male and female RECs and inflammation in patients with SSHTN. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Butler et al. (Fri,) conducted a other in Salt-sensitive hypertension. N(G)-Nitro-L-arginine-methyl ester (LN) / high salt diet (HS) protocol vs. Male vs Female was evaluated on Blood pressure, glomerular filtration rate, and immune cell infiltration (p=<0.05). Female sex in a mouse model of salt-sensitive hypertension was associated with greater increases in blood pressure and significant reductions in glomerular filtration rate compared to males (p<0.05).