Effects of an Acute Vitamin C Infusion on Neurovascular Coupling in Healthy Adults
Authors: DeConne Theodore Mark , Sanjana Faria , Nichols Wendy , Hobson Joshua Charles , Martens Christopher R 
Published: June 2021

Increases in neuronal metabolic demand are typically matched by a proportional increase in brain blood flow. This neurovascular coupling (NVC) response is impaired with healthy aging and in Alzheimer's disease and has been attributed to an imbalance of reactive oxygen species (ROS) relative to endogenous antioxidant defenses (oxidative stress) in animal models; however, the role of ROS on NVC in healthy humans is not completely understood. High levels of ROS in the vasculature impairs endothelium‐dependent vasodilatation whereas smaller amounts of ROS in neurons may be necessary for NVC. Therefore, we aimed to investigate the effect of an acute antioxidant infusion (vitamin C; VTC) on NVC and shear‐mediated dilation of the internal carotid artery (ICA) in healthy adults. We hypothesized that, compared with control (saline), acute infusion of the antioxidant VTC would augment NVC in healthy adults. Seven healthy adults (2 males/5 females, age: 38 ± 24 years; BMI: 24.0 ± 3.5 kg/m2; blood pressure (BP): 104 ± 8/62 ± 5 mmHg) participated in this randomized, double‐blind placebo‐controlled intervention. Participants received a 20‐minute priming bolus infusion of either saline or 0.06 g ascorbic acid per kg fat‐free mass (FFM), followed by a drip‐infusion of either saline or 0.02 g ascorbic acid per kg FFM. Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler (TCD) ultrasound (Spencer Technologies, Redmond, WA) at an average insonation depth of 48.0 ± 6.0 mm. Cerebrovascular conductance (CVC) was calculated as mean MCAV divided by beat‐beat mean arterial pressure (FINAPRES NOVA, Enschede, Netherlands). NVC was assessed as the percent change (from baseline) in CVC (CVC%Δ) during an incrementally difficult cognitive challenge (N‐back task) after acute infusion of VTC vs. saline. Shear‐mediated vasodilation of the ICA to a transient (30 second) hypercapnia stimulus was also assessed at each time point as a measure of vascular function independent of neuronal demand. To quantify the NVC response, post infusion CVC and performance at each stage of the N‐back test were analyzed using a 2×2 repeated measures ANOVA with treatment (saline vs. VTC) and stage of the N‐back test as factors. Post‐infusion vasodilation of the ICA to transient hypercapnia was analyzed between treatment conditions using a paired t‐test. Data are presented as mean ± SD. Post‐infusion CVC%Δ was blunted at all levels of the N‐Back task after the infusion of VTC vs. saline (0‐Back: −3.94 ± 7.23% vs. 0.95 ± 3.23%; 1‐Back,: −4.16 ± 8.15% vs. 2.23 ± 4.72%; 2‐Back: −4.83 ± 14.94% vs. 4.79 ± 6.13%; Treatment effect: P = 0.045; F‐statistic (1,18) = 4.66). While there were no significant differences between stages, the number of correct responses decreased as the difficulty of the test increased. No significant differences in the ICA response to transient hypercapnia were observed after infusion of VTC vs. saline (4.08 ± 1.44% vs. 4.62 ± 0.76%; P = 0.54). These data suggest that ROS may be necessary to elicit an appropriate NVC response in healthy adults.Support or Funding InformationThis work was supported by a pilot grant through the Center of Biomedical Research Excellence in Cardiovascular Health P20GM113125.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.