Evidence for an inflammatory contribution to cutaneous microvascular endothelial dysfunction in non-Hispanic Black women

Non-Hispanic Black (NHB) adults demonstrate impaired microvascular endothelial function, characterized as reduced nitric oxide (NO)-mediated vasodilation, compared to non-Hispanic White adults. A sexual dimorphism exists, where microvascular dysfunction is mediated through elevated superoxide generation in NHB men but not NHB women. Inflammatory mechanisms in NHB women may contribute, but these mechanisms have not been explored in vivo. We hypothesized that micro- and macrovascular function would improve after oral salsalate [nuclear factor kappa B (NF-κB) activation inhibitor] in NHB women. After placebo or salsalate (1,500 mg twice a day, 5 days), two intradermal microdialysis fibers were placed in 13 NHB women [28 (7) yr]. Local heating units (33°C) and laser-Doppler flowmetry (flux) probes were placed over each fiber. Increasing concentrations of acetylcholine were perfused alone (ACh; dissolved in lactated Ringer's) or with NG-nitro-l-arginine methyl ester (ACh+l-NAME). Cutaneous vascular conductance was calculated (CVC = flux × mmHg-1) and normalized to site-specific maximum (28 mM sodium nitroprusside + 43°C). Macrovascular endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and handgrip-augmented FMD (FMD+HG). Salsalate treatment did not impact ACh-induced vasodilation overall (main effect, P = 0.24), but a treatment × site interaction effect emerged (P < 0.0001). ACh increased and ACh+l-NAME decreased after salsalate (both P ≤ 0.03), but this effect was small (Cohen's f = 0.19). Five-day salsalate treatment did not alter %FMD (P = 0.28) or %FMD+HG (P = 0.17). Cutaneous microvascular, but not macrovascular, function marginally improved after salsalate, indicating that inflammation via NF-κB pathways contributes to impaired cutaneous microvascular function in NHB women.NEW & NOTEWORTHY Our results show that cutaneous microvascular, but not macrovascular, function is improved after oral salsalate treatment in healthy non-Hispanic Black women. These data reveal that systemic inflammation via NF-κB pathways attenuates cutaneous microvascular function in this population.