Blood pressure variability compromises vascular function in middle-aged mice

Blood pressure variability (BPV) has emerged as a significant risk factor for cognitive decline and dementia, independent of alterations in average blood pressure (BP). However, the impact of large BP fluctuations on neurovascular function remains poorly understood. In this study, we developed a novel murine model of BPV in middle-aged mice using intermittent Angiotensin II infusions. Radio telemetry confirmed that 24-hr BP averages in BPV mice remained comparable to controls, demonstrating BPV in the absence of hypertension. Chronic (20-25 days) BPV resulted in a blunted bradycardic response and cognitive deficits. Two-photon imaging revealed heightened pressure-evoked constrictions (myogenic response) in parenchymal arterioles of BPV mice. While sensory stimulus-evoked dilations (neurovascular coupling) were amplified at higher BP levels in control mice, this pressure-dependent effect was abolished in BPV mice. Our findings indicate that chronic BP fluctuations impair vascular function within the neurovascular complex and contribute to cognitive decline, emphasizing BPV as a critical factor in brain health.