The endothelial mineralocorticoid receptor mediates the neurovascular coupling response during angiotensin II-hypertension

Hypertension, a leading risk factor for vascular contributions to cognitive impairment and dementia (VCID), impairs cerebral artery structure and function. We have linked hyperaldosteronism or mineralocorticoid receptor (MR) activation to cerebrovascular damage and VCID development. MR antagonists reverse hypertension-associated cerebral parenchymal arteriole (PA) remodeling, impaired endothelium-dependent dilation, and cognitive decline. However, the MR is widely expressed in the cerebral vasculature, making it difficult to determine which cell type is responsible for the improvements. In a mouse model of Angiotensin II (AngII)-induced hypertension, we found that endothelial cell (EC)-MR deletion corrected impaired PA endothelium-dependent dilation, but, interestingly, cognitive dysfunction was not corrected by EC-MR deletion (unpublished). Neurovascular coupling (NVC) is a sophisticated vascular response that is essential to perfusion and cognition. The NVC response links neuronal activity and metabolic demand to increase local cerebral blood flow (CBF), but this process is impaired in hypertension. To continue investigating the role of the EC-MR in cerebrovascular dysfunction, we tested the hypothesis that AngII mice exhibit impaired neurovascular coupling (NVC) mediated by EC-MR activation. 16-18-week-old MR-intact and ECMR knockout (ECMRKO) male mice were treated with AngII (800ng/kg/min) for 4 weeks; sham-operated mice served as controls. NVC was assessed via a whisker stimulus, and the %change in CBF was measured in the contralateral whisker barrel cortex using laser speckle contrast imaging. An ipsilateral whisker stimulation was performed as a control. Data are presented as mean ± SEM; n=5-8 per group. MR-intact AngII mice had a blunted increase in CBF in response to a whisker stimulation compared to MR-intact mice (8.50%±0.8 vs. 3.07%±0.6, MR-intact+Sham vs. MR-intact+AngII, p< 0.01; n=7-8), which demonstrates impaired NVC in hypertension. ECMRKO mice treated with AngII had a greater %increase in CBF compared to MR-intact+AngII mice (3.07%±0.6 vs. 8.95%±1.2, MR-intact+AngII vs. ECMRKO+AngII, p=0.02; n=6-7). There was no difference in the NVC response between the ECMRKO sham and ECMRKO+AngII mice (8.85%±1.4 vs. 8.95%±1.2, ECMRKO+Sham vs. ECMRKO+AngII, p>0.999; n=5-6). Our data show that EC-MR signaling contributes to hypertension-associated impaired NVC and PA endothelium-dependent dilation to suggest that the MR is a potential therapeutic target to improve cerebrovascular function during hypertension. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.