THE SENOLYTIC QUERCETIN PREVENTS AGE-ASSOCIATED VASCULAR STIFFENING, REDUCES BLOOD PRESSURE AND IMPROVES COGNITIVE FUNCTION IN DAHL SALT-SENSITIVE RATS CONSUMING A NORMAL SALT DIET

Abstract

Objective: Quercetin (QRC), a flavonoid with anti-oxidant, anti-inflammatory and senolytic effects, reduced BP in salt-induced hypertension in Dahl salt-sensitive (DSS) rats. The increases in central arterial stiffness (CAS) and blood pressure (BP) occur, as manifestation of early vascular aging (EVA), in DSS rats even consuming a normal salt (NS) diet, moreover, EVA is associated with cognitive impairment in humans. We hypothesized that as age advances, a decline in cognitive function will accompany EVA in DSS rats consuming a NS diet, and that QRC will not only retard EVA, but also will improve cognitive function. Design and method: A NS diet (0.5% NaCl), supplemented with QRC (100 mg/kg BW/day) was administered to male DSS rats at 6-mo of age (n=24) for a 3-month period. DSS without QRC supplementation served as a control group (n=12). Systolic and diastolic BP (SBP, DBP), pulse wave velocity (PWV, an index of CAS), echocardiography, and a visuospatial attention test were assessed prior to and following QRC treatment. Results: At 6-mo of age none of the measured parameters differ between control and QRC rats. During aging from 6- to 9-mo in the control group, SBP, DBP and PWV significantly increased, ESLV.vol showed a statistically borderline trend to increase, HR and EF showed a statistically borderline trend to decrease, and attention behavior did not change. QRC treatment reduced SBP, PWV, and ESLV.vol, and increased EF and attention (Table). The QRC effect to increase the number of correct attention test responses was inversely correlated with PWV (Pearson r=-0.420, P=0.02) but not with BP or cardiac parameters, indicating that CAS but not BP is linked to cognitive function. Conclusions: QRC reduces EVA and improves cognition assessed as an attention behavior. Although both BP and CAS are manifestations of EVA, a positive association between attention decline with PWV, but not BP, suggests that CAS is linked to cognitive function via mechanisms that are not directly related to BP. Further studies are required to determine whether the effects of QRC on EVA in DSS rats, consuming a NS diet, are linked to its anti-oxidant, anti-inflammatory or senolytic properties.