Impairment of Neurovascular Coupling by Chronic Stress

Abstract

Chronic stress (CS) is a contributory factor in a wide range of diseases. To date, no studies have focused on the effects of chronic stress on neurovascular coupling (NVC). NVC matches neuronal activity with an increase in local blood flow, ensuring that the metabolic demands of the active tissue are satisfied.We studied NVC in a rat model of CS. Rats were exposed to one of 5 stressors each day for 7 days; we have previously shown that this produces an anxious behavioral phenotype. NVC was impaired by CS: vasodilation of parenchymal arterioles evoked by electrical field stimulation in brain slices was greatly reduced, whereas evoked astrocyte endfoot [Ca2+] was enhanced. In isolated amygdalar arterioles of CS rats, dilation evoked by increasing [K+]o was diminished, suggesting an impairment of inward‐rectifier K+ (Kir) channels. In myocytes from CS rats we observed a decrease in Kir current density. Corticosterone delivery produced a similar NVC phenotype to CS, suggesting that this molecule might mediate NVC impairment. These data suggest that CS causes a decrease in Kir channel number in myocytes of amygdalar parenchymal arterioles, possibly through the actions of corticosterone, rendering the vessel less able to respond to small increases in [K+]o released from astrocyte endfeet and resulting in impaired vasodilation after neuronal activity. This impairment may contribute to CNS disorders with a stress component.