High fat diet‐induced obesity promotes cerebrovascular autoregulatory dysfunction in aged mice

Abstract

Diet‐induced obesity in the elderly promotes the development of vascular cognitive impairment, which develops in the absence of Alzheimer‐type senile plaques as a result of decreased cerebral blood flow due to vascular alterations. To test the hypothesis that obesity in aging impairs local vasoregulatory mechanisms in cerebral arteries, young (3 mo) and aged (24 mo) C57BL/6 mice were fed a high fat diet (HFD) or a standard diet (SD) for 6 months. In middle cerebral arteries (MCA) isolated from obese aged mice stepwise increases in transmural pressure (from 10 to 160 mmHg) elicited impaired steady‐state myogenic constriction as compared to responses obtained in vessels of young SD‐ and HFD‐fed and aged SD‐fed mice. MCAs from aged obese mice also exhibited impaired dynamic myogenic responses and flow‐induced constriction. Furthermore, obesity impaired metabolic vasodilation in response to adenosine in young mice, whereas its effect was exacerbated in aged mice. Collectively, aging exacerbates obesity‐induced cerebrovascular autoregulatory dysfunction, which likely promotes microvascular damage contributing to the development of vascular cognitive impairment in aged obese individuals. (Funding: AHA, AFAR, NIH).