Age-related Blood Pressure Increase is Associated with Elevated Sympathetic Nerve Activity in C57BL/6J Male Mice

Aging is a significant risk factor for cardiovascular diseases, including hypertension and heart failure. Previous studies in our laboratory have demonstrated that in aging, senescent glial cells accumulate in the key brainstem region regulating cardiovascular function, such as the rostral ventrolateral medulla (RVLM). Senescent glial cells are known to secrete senescence-associated secretory phenotype (SASP) factors causing neuroinflammation, which could lead to sympathoexcitation. While elevated sympathetic nerve activity (SNA) has been implicated in neurogenic hypertension in obesity, its relevance to age-related blood pressure increase is not clear. Hence, we hypothesized that aging contributes to increases in blood pressure mediated through increase in sympathetic nerve activity. To address this hypothesis, young (3 months, n=4) and aged C57BL/6J male mice (18-24 months, n=4) on regular chow diet were surgically implanted with radiotelemetric devices in their carotid artery for continuous monitoring of blood pressure and heart rate. After seven days of recovery period, blood pressure and heart rate data were collected from conscious, unrestrained mice on a normal chow diet continuously for a period of 48 hrs. Data were analyzed by unpaired student’s t-test and expressed as mean ± S.E. Aged mice exhibited higher systolic blood pressure (SBP) (127.3 ± 2.29 vs 106.21 ± 4.17 mmHg, p < 0.005), diastolic blood pressure (DBP) (98.23 ± 4.23 vs 84.53 ± 2.65 mmHg, p < 0.05), and mean arterial pressure (MAP) (112.81 ± 2.97 vs 95.39 ± 3.09 mmHg, p < 0.01), compared to the young mice. To assess SNA, mice were administered intraperitoneally with ganglionic blocker, hexamethonium and changes in mean arterial pressure (MAP) were recorded. Aged mice displayed a greater depressor response (-47.10 ± 2.59 vs -12.09 ± 1.16, p < 0.0001), compared to the young mice following hexamethonium injection, indicating significantly elevated sympathetic nerve activity. These findings confirm that elevated SNA could contribute to aging-related hypertension. Future studies will identify glial cell-type specific mechanisms in the brainstem that contributes to age-related sympathoexcitation and increased risk for cardiovascular diseases. NHLBI-NIGMS R01HL163775 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.