Quercetin Alleviates Age-Related Cardiovascular Decline and Links Cardiac Remodeling to Cognitive Performance in Dahl Salt-sensitive Female Rats

Background: It is established that cardiovascular risk factors, high blood pressure (BP) and central arterial stiffness (CAS), e.g. early vascular aging (EVA), are associated with vascular and degenerative brain damage and an increased risk of cognitive decline and dementia. EVA and cognitive impairment occur in Dahl salt-sensitive (DSS) rats consuming a normal salt (NS) diet with an advancing age. Previously we demonstrated that senolytic quercetin (QRC), a flavonoid with antioxidant and anti-inflammatory properties, reduced EVA and improved cognitive function in adult DSS male. We hypothesized that QRC will exhibit similar effect, i.e., will reduce EVA and improve cognitive function in DSS females consuming NS diet. Methods: A NS diet (0.5% NaCl), supplemented with QRC (100 mg/kg BW/day) was administered to female DSS rats at 6-mo of age (n=25) for a 3-month period. DSS rats without dietary supplementation of QRC served as a control group (n=11). Systolic BP (SBP), pulse wave velocity (PWV, an index of CAS), echocardiography, and cognitive function, assessed by a visuospatial attention test were assessed prior to and following QRC treatment or placebo. Results: At 6-mo of age none of the measured parameters differed between control and QRC treated rats. During three-month period from 6- to 9-mo of age, SBP, and PWV and relative left ventricular wall thickness (LV-RWT) significantly increased, and attention behavior did not change in the control group. QRC treatment abrogated age-related increasing of SBP, PWV, and RWT, but it did not affect cognitive function assessed by the number of correct responses to visual stimulus (Table). However, in QRC group, the number of correct attention test responses inversely correlated with LV-RWT (Pearson r=-0.543, P=0.011), and positively borderline correlated with cardiac output (Pearson r=0.385, P=0.085) and stroke volume (Pearson r=0.409, P=0.059), indicating that heart structural and functional parameters have strong link with cognitive function. Conclusions: Chronic 3-month dietary treatment with QRC, an antioxidant and anti-inflammatory compound, effectively mitigated EVA and protected heart, but did not affect cognitive function in DSS females. However, better attention was associated with the improved heart parameters in QRC group, suggesting a potential link between cardiac remodeling and attentional performance in the aged female DSS rats. Table. Effect of Quercetin (QRC) on Behavioral and Cardiovascular Parameters in a DSS Rat Model of Early Vascular Aging. [Table: see text] Values are expressed as mean ± standard deviation. Data were analyzed by 2-way ANOVA with repeated measurements followed by Sidak’s post-test. p<0.05 was considered significant. * P < 0.05 vs. 6-mo correspondent group; † p<0.05 vs. control group at correspondent age. Supported by NIA/NIH/IRP 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.