Glucocorticoid signaling mediates stress‐induced impairment of neurovascular coupling (841.4)

Stress influences the progression and severity of many diseases. Here we examined the effects of stress on neurovascular coupling (NVC), which matches cerebral blood flow increases to local neuronal activity. NVC was studied in brain slices from the amygdala, where dilation of parenchymal arterioles (PAs) was measured in response to neuronal stimulation. We administered a 7‐day stress paradigm to male Sprague‐Dawley rats, resulting in anxiety‐like behavior and attenuated weight gain. After stress, PA vasodilation evoked by neuronal stimulation was reduced by 66%. This reduction was similar to that previously reported for the effect of blocking inward rectifier K + (Kir) channels during NVC 1 . Indeed, blocking Kir channels with barium inhibited NVC in control but not stressed slices. We thus hypothesized that the impairment of NVC by stress reflects a loss of PA Kir channels. Consistent with this, we found that Kir channel current density in smooth muscle cells from PAs was reduced by 90%. Moreover, elevation of external K + from 3 to 8 mM, which normally causes profound dilation of PAs through Kir activation, was almost without effect on arterioles from stressed rats. In vivo delivery of corticosterone (without stressors) or the glucocorticoid receptor blocker RU486 (prior to stressors) mimicked or prevented NVC impairment by stress, respectively. We conclude that stress causes a glucocorticoid‐mediated decrease in functional Kir channels in PA myocytes in the amygdala. This renders arterioles less responsive to K + released from endfeet during NVC, thus impairing vasorelaxation. These studies may pave the way for the development of novel treatment options for brain disorders with a stress component. 1. Filosa et al . (2006) Nat Neurosci 9(11): 1397‐1403 Grant Funding Source : Supported by National Institutes of Health and the American Heart Association.