Reduced Cutaneous Nitric Oxide-Mediated Vasodilation of the Microvasculature in the Paretic Leg of Individuals Post-Stroke

Background: In stroke survivors poor blood flow delivery to exercising skeletal muscle due to impaired vasodilation of the microvasculature could negatively influence motor function and stroke rehabilitation outcomes. The objective of this study was to, 1) examine peak endothelium-dependent vasodilation of the cutaneous microvasculature of chronic stroke survivors via local infusions of acetylcholine (ACh), and 2) determine the nitric oxide (NO)-mediated component of the dilator response via infusion ofNG-nitro-L-arginine methyl ester (L-NAME), an endothelial nitric oxide synthase inhibitor. We hypothesized peak endothelium-dependent and NO-mediated vasodilation would be lower in the paretic vs. non-paretic leg and vs. the dominant leg of neurologically intact controls (CON). Methods: This is a preliminary analysis of an ongoing clinical trial (NCT06027294). Microdialysis catheters (2 per leg) were inserted into the dermal layer of the paretic and non-paretic thigh of individuals post-stroke and the dominant thigh of CON. Laser doppler flowmetry probes with integrated heaters (clamped at 33°C) were placed above the catheters. Participants rested for 60 min while Ringer’s solution ± L-NAME (10 mM) was infused (2 µL/minute). Baseline values were recorded prior to infusions of ACh at all sites (10 -10 M – 10 -1 M; 5-minutes per dose). Maximum vasodilation was assessed via heating (43°C) and infusion of sodium nitroprusside (SNP; 28 mM). Flux was averaged over the final minute of each dose and percent change in cutaneous vascular conductance was calculated: ((flux / mean arterial pressure) / (max flux) * 100). NO-mediated vasodilation was calculated as the difference between ACh ± L-NAME. Walking speed was assessed using the 10-meter walk test. Results: Ten individuals post-stroke (age 62 ± 15 years, 50% female, 11± 9 years post-stroke) and four CON (age 59 ± 12 years, 25% female) have completed the study. Peak endothelium-dependent vasodilation was not different between the paretic vs. non-paretic leg (x = 80 ± 23% vs. 79 ± 22%, p = 0.29) or paretic vs. CON leg (x = 83 ± 18%, p = 0.42). NO-mediated vasodilation was reduced in the paretic vs. non-paretic leg (x = 6 ± 30% vs. 22 ± 32%, p = 0.02) as well as in the paretic vs CON leg (x = 46 ± 20%, p = 0.02). There was a positive association between peak endothelium-dependent vasodilation and walking speed (r = 0.78, p = 0.01) but not between NO-mediated vasodilation and walking speed (r = 0.35, p = 0.36). Conclusion: Peak endothelium-dependent vasodilation to ACh in the cutaneous microvasculature was similar between the legs of chronic stroke survivors and vs. CON. However, NO-mediated vasodilation was reduced in the paretic leg, potentially due to limb-specific pathology. The paretic leg’s endothelium-dependent vasodilation may have an influence on gross motor function shown by its preliminary association with walking speed. We are continuing to collect data in stroke survivors (n = 20) and age- and sex-matched controls (n = 20). Funding: AAW was supported by NHLBI (T32HL13464) and Cardiovascular Center’s A.O. Smith Fellowship Scholars Program. Research was supported by NICHD (R01-HD112258). This abstract was presented at the American Physiology Summit 2025 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.