The functional integrity of the brain depends on a tight coupling between neuronal activity and local cerebral blood flow, a process known as neurovascular coupling (NVC). This mechanism ensures the timely delivery of oxygen and metabolic substrates to active neuronal circuits. Nitric oxide (NO), produced through the glutamate–NMDAr–nNOS–sGC pathway, is a key mediator of communication between neurons and the cerebral vasculature. Under physiological conditions, tightly controlled redox signaling preserves NO bioavailability and supports efficient NVC. Conversely, disruption of redox homeostasis reduces NO bioavailability which is linked to NVC impairment and cognitive decline in different pathological conditions (e.g. Alzheimer’s disease, vascular cognitive impairment and type 2 diabetes). Understanding how redox mechanisms regulate NO signaling within the neurovascular unit is therefore critical for identifying strategies capable of preserving cerebrovascular function and cognitive health. Among these, dietary inorganic nitrate—abundant in vegetables such as beetroot and green leafy vegetables—has emerged as a promising approach to enhance NO bioavailability.

To explore the interplay between redox regulation, NO signaling, neurovascular coupling and cognition, we investigated rodent models of vascular cognitive impairment, including chronic cerebral hypoperfusion (2VO) and type 2 diabetes. Using a multimodal approach combining behavioral testing, in vivo assessment of NVC and cerebral blood flow dynamics, magnetic resonance imaging, and molecular analyses of vascular remodeling and oxidative stress pathways, we demonstrate that these models exhibit marked neurovascular dysfunction accompanied by oxidative stress–driven redox imbalance and impaired spatial learning and memory. Importantly, boosting NO bioavailability through dietary nitrate was able to improve NVC responses, improved cerebral blood flow regulation, attenuated pathological vascular remodeling, and improved cognitive performance. Together, these findings highlight the central role of redox-dependent regulation of NO signaling in maintaining neurovascular coupling in health and its disruption in disease.