Blood pressure variability compromises vascular function in middle-aged mice

Blood pressure variability (BPV) has emerged as a novel risk factor for cognitive decline and dementia, independent of alterations in average blood pressure (BP). However, the underlying consequences of large BP fluctuations on the neurovascular complex are unknown. We developed a novel mouse model of BPV in middle-aged mice based on intermittent Angiotensin II infusions. Using radio telemetry, we demonstrated that the 24-hr BP averages of these mice were similar to controls, indicating BPV without hypertension. Chronic (20-25 days) BPV led to a blunted bradycardic response and cognitive deficits. Two-photon imaging of parenchymal arterioles showed enhanced pressure-evoked constrictions (myogenic response) in BPV mice. Sensory stimulus-evoked dilations (neurovascular coupling) were greater at higher BP levels in control mice, but this pressure-dependence was lost in BPV mice. Our findings support the notion that large BP variations impair vascular function at the neurovascular complex and contribute to cognitive decline.