Sex differences in the progression of salt-sensitive hypertension in aged Dahl salt-sensitive rats

Salt-sensitive hypertension is a major cardiovascular risk factor that is exacerbated by aging. Emerging evidence suggests complex mechanistic pathways involving renal sodium handling, vascular dysfunction, and hormonal alterations that vary by sex and age. The Dahl salt-sensitive (SS) rat model provides an excellent platform for investigating age-related changes in blood pressure regulation under high-salt conditions. This study examined the development of salt-sensitive hypertension in aged Dahl SS rats (>30 wk old; both males and females), focusing on sex differences in survival and blood pressure. Female animals were further categorized by breeding status (breeder vs. nonbreeder) to evaluate the effects of reproductive history on cardiovascular outcomes. Male and female rats demonstrated similar overall survival rates (60%) during the high-salt challenge, although mortality occurred earlier in females. Males exhibited lower baseline mean arterial pressure compared with females. No significant differences were observed between breeder and nonbreeder females in survival, blood pressure, or heart rate. Circadian rhythm analysis revealed that females had a higher mesor before high-salt exposure and a shifted acrophase during the first 4 days of the diet. Urinary cystatin C increased significantly in females but not in males following high-salt exposure. Overall, aged female rats exhibited higher baseline cardiovascular parameters, including blood pressure and heart-to-body weight ratio (HBW), and greater renal stress responses (cystatin C and electrolyte excretion) than males, despite similar survival rates. These findings provide new insights into sex-specific cardiovascular and renal responses to salt loading in aging and may help explain sex-dependent differences in salt-sensitive hypertension.NEW & NOTEWORTHY Using aged Dahl salt-sensitive rats, this study examines how aging, sex, and reproductive history influence salt-sensitive hypertension. Reproductive history did not affect cardiovascular outcomes in aged females. Integrated survival analysis, circadian blood pressure monitoring, and renal biomarkers reveal sex-specific responses to high-salt intake, providing new insights into mechanisms contributing to salt-sensitive hypertension in aging.