Elevated Plasma Aldosterone Impairs Functional Hyperemia and Cognitive Function

Aldosterone, a steroid hormone, plays an important role in blood pressure homeostasis and the maintenance of plasma electrolyte levels by activating the mineralocorticoid receptor (MR) in renal distal tubule and collecting duct epithelial cells. Recent studies revealed that MRs are also expressed in other tissues, including cardiac myocytes, vascular smooth muscle cells, and vascular endothelial cells (EC), and that elevated plasma aldosterone, termed hyperaldosteronemia (HA), has deleterious effects on the cardiovascular system. HA is present in 10-30% of hypertensive patients and unrecognized and asymptomatic HA is estimated to occur in > 10% of individuals with normal blood pressure. Despite the high prevalence of HA, little is known about its impact on cerebral blood flow (CBF) regulation and brain health. This study focused on the physiological processes that support the on-demand delivery of blood to regions of heightened neuronal activity (functional hyperemia). Specifically, we examined the impact of HA on the recently discovered novel mechanism, termed capillary-to-arteriole signaling, through which capillaries and their strong inward rectifier K+ (Kir 2.1) channels play a significant role in functional hyperemia. Importantly, early deficits in functional hyperemia are a hallmark of small vessel diseases of the brain, which are significant contributors to cognitive impairment and dementia. Employing HA model mice, we examined the impact of HA on functional hyperemia, capillary-to-arteriole signaling, Kir2.1 channel activity in freshly isolated capillary ECs (cECs), and cognitive function. Functional hyperemia, measured as whisker stimulation-induced CBF increases using laser Doppler flowmetry, was impaired in HA animals compared to vehicle-treated animals. Retrograde capillary-to-arteriole signaling, evaluated as upstream arteriolar dilation in response to capillary stimulation with 10 mM K+ in Capillary-Parenchymal Arteriole (CaPA), preparations was significantly attenuated in HA mice. Furthermore, cEC Kir2.1 channel currents, recorded using the conventional whole-cell configuration of the patch-clamp technique, were significantly smaller in HA mice compared to vehicle-treated mice. Further, HA model animals obtained lower scores in the Novel Object Recognition test, indicating that cognitive function in the form of memory retention may be impacted by elevated plasma aldosterone. These data suggest that HA impairs functional hyperemia and cognitive function, and that HA may be a novel risk factor for vascular cognitive impairment. This work was supported by The National Institute of Health (P20-GM-135007 to MK and R01-HL-142888 to GCW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.