Rodents Exposed to an Impoverished Environment Display Sex Differences in Blood Pressure, Brain and Kidney Inflammation in Adulthood

Introduction: Poverty, a low-resourced state, is a common adverse childhood experience (ACE) or early life stress (ELS) that affects ~333 million children worldwide. People that experienced childhood poverty are at greater risk for developing hypertension (HTN) during adulthood, with sex differences. Multiple human and animal models of HTN display a strong positive correlation with inflammation and blood pressure (BP). However, this association is not widely examined in rodents that have experienced an impoverished environment. The objective of this study is to investigate the changes in BP, parasympathetic activity, and inflammation in the brain and kidneys of rodents exposed to an impoverished environment, using the limited bedding and nesting (LBN) model. We hypothesize that LBN males (M) will display an increase in BP, pro-inflammatory cytokines, and decrease in high frequency heart rate variability (HF HRV; parasympathetic activity) compared to control (CON) M. LBN females (F) will display no changes in these parameters compared to CON F. Methods: The LBN model mimics childhood poverty by creating an impoverished environment with a reduction of bedding and nesting material on postnatal days 2-9. The LBN rats had ~80% less bedding and nesting material compared to the CON. After weaning, the offspring were separated by sex and treatment: LBN M (n=8), CON M (n=8), LBN F (n=8), and CON F (n=8). Using colorimetric assays, tumor necrotic factor-alpha (TNF-α) and interleukin-17 (IL-17) were measured in the brain (cerebrum, brain stem, and cerebellum) and kidney (cortex and medulla) of adult LBN and CON rats at 16-18 weeks of age. Results: LBN M displayed an increase in BP (140 ± 3 vs 117 ± 5 mmHg; p=0.001) compared to CON M. LBN F had no changes in BP vs CON F (ns). HF HRV was increased in both LBN groups vs CON (F (1, 25) = 4.408; p=0.05). IL-17 in the cerebrum (1.93 ± 0.13 vs 2.96 ± 0.34 mg/mL/mg protein; p=0.02) and brain stem (2.04 ± 0.35 vs 4.43 ± 1.23 mg/mL/mg protein; p=0.04) were decreased in LBN M vs CON M. Furthermore, TNF-α was decreased in the cerebrum (268.81 ± 17.99 vs 334.28 ± 20.91 pg/mL/mg protein; p=0.04), brain stem (90.26 ± 19.65 vs 166.52 ± 16.59 pg/mL/mg protein; p=0.04), and cerebellum (71.90 ± 16.43 vs 206.79 ± 73.65 pg/mL/mg protein; p=0.04) of LBN M vs CON M. No changes in brain IL-17 or TNF-α were observed in LBN F vs CON F (ns). The kidney cortex and medulla showed no changes in IL-17 and TNF-α in LBN vs CON and/or M vs F (ns). Conclusion: LBN F revealed no changes in BP and inflammation in the brain and kidneys. Parasympathetic activity (HF HRV) was increased in LBN M and LBN F rats. Despite the increase in parasympathetic activity, LBN M exhibited an elevation in BP and surprisingly a decrease in IL-17 & TNF-α in the brain. Perhaps, the increase in parasympathetic activity and decrease in pro-inflammatory cytokines are working together to lower BP. Contrarily, the increase in parasympathetic activity alone in LBN F may blunt the increase in BP expected with LBN treatment. Future studies are warranted to understand these sex differences. This study helps to elucidate the pathogenesis and etiology of HTN, and to provide insights into possible sex-specific therapeutic targets to improve the BP of people that encountered an ACE, such as childhood poverty. Funding: This research received no specific grant from any funding agency but was funded by PI’s (MWCJr) startup funds. This abstract was presented at the American Physiology Summit 2025 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.