What is the clinical evidence from this study?

Study design: Other. Population: Salt-sensitive hypertension. Intervention: High-salt challenge vs. Sex (males vs. females). Primary outcome: Overall survival.

What does this research mean for the field?

In aged Dahl salt-sensitive rats, females exhibit higher baseline cardiovascular parameters and greater renal stress responses to high-salt diets compared to males, despite having similar overall survival rates. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

May 26, 2026

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

Key Result

Aged female Dahl salt-sensitive rats exhibited higher baseline cardiovascular parameters and greater renal stress responses to a high-salt challenge than males, despite similar 60% survival rates.

Key Points

To investigate sex differences in the progression of salt-sensitive hypertension in aged Dahl salt-sensitive rats and the effects of reproductive status.
Examined aged Dahl SS rats (≥30 weeks old) for survival and blood pressure under high-salt conditions.
Categorized females by breeding status to evaluate reproductive history's impact on cardiovascular outcomes.
Performed circadian rhythm analysis and measured urinary cystatin C and electrolyte excretion.
Both male and female rats had similar survival rates (60%), but females experienced earlier mortality.
Males had lower baseline mean arterial pressure than females, while females showed greater cardiovascular parameters post-exposure.
Urinary cystatin C increased significantly in females following high-salt exposure, indicating greater renal stress.

Structured PICO

Population

Aged Dahl salt-sensitive (SS) rats (>30 weeks old; both males and females)

Intervention

High-salt diet/challenge

Comparator

Sex (males vs. females) and reproductive history in females (breeder vs. non-breeder)

Outcome

Survival and blood pressuresurrogate

Aged female Dahl salt-sensitive rats exhibit higher baseline cardiovascular parameters and greater renal stress responses to salt loading compared to males, despite similar survival rates.

Main Result

Absolute Event Rate: 60% vs 60%

Abstract

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 weeks old; both males and females), focusing on sex differences in survival and blood pressure. Female animals were further categorized by breeding status (breeder vs. non-breeder) 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 non-breeder females in survival, blood pressure, or heart rate. Circadian rhythm analysis revealed that females had a higher mesor prior to high-salt exposure and a shifted acrophase during the first four 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) 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.

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