Abstract Body: Introduction: Blood pressure variability (BPV) is a novel risk factor for cognitive decline with poorly defined mechanisms. Whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is unknown. Using a recently established model of BPV, this study explores the impact of BPV and HSD on physiological pathways underlying systemic BP regulation (baroreceptor reflex) and cerebral blood flow (myogenic and functional hyperemia (FH) responses).
Hypothesis: We tested the hypothesis that a HSD exacerbates BPV-induced cardiovascular and neurovascular dysfunction, contributing to the early onset of cognitive decline
Methods: Male C57Bl6 (12-15-month-old) mice were implanted with a cranial window and telemetry for in-vivo two-photon (2P) imaging and BP measurement, respectivley. A programmable pump delivered 2 μL of saline (Control:Ctrl) or angiotensin II (Ang II 18 μg/day) (BPV) intermittently every 3-4hrs subcutaneously for 25 days. A separate cohort of Ctrl and BPV mice received a high salt diet (HSD; 4% NaCl chow+1% NaCl drinking water: Ctrl fed HSD=C+H and BPV fed HSD=B+H.
Results: Ang II infusion increased BPV index (P<0.01,n=8) at day 3 of treatment which was sustained through the treatment period. While the Ctrl, BPV, and C+H groups did not develop hypertension, B+H mice had a significant increase in 24hr MAP (Δ29±4 mmHg, P<0.01, n=6) following 20 days of treatment. Linear regression analysis of systolic BP vs heart rate showed blunted bradycardic responses in BPV (P<0.01,n=8) which was exacerbated in B+H mice (P<0.01, n=6). B+H mice had a higher mortality rate of 37% vs 12% and 0% in BPV and C+H, respectively. Preliminary 2P data showed enhanced myogenic response in parenchymal arterioles of B+H vs Ctrl (P=0.01,n=3 runs) and trended to be higher than those in BPV. Whisker stimulation evoked FH in Ctrl (P<0.01, n=8) and BPV (P<0.01, n=7); however preliminary data show no dilatory response to WS in B+H (P=0.5, n=2).
Conclusions: These data showed that a high-salt diet caused hypertension in C57Bl6 mice only when combined with blood pressure variability. The comorbidities of HSD and BPV also blunted the baroreceptor reflex response and increased mortality. Preliminary data suggest that HSD in the presence of BPV induces enhanced myogenic reactivity of parenchymal arterioles and a blunted neurovascular coupling response. Ongoing studies are evaluating the comorbid effects of B+H on cognitive function.