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

Abstract

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 in NHB men 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 following oral salsalate [nuclear factor kappa B (NF-κB) activation inhibitor] in NHB women. Following placebo or salsalate (1500 mg, b.i.d., 5 days), two intradermal microdialysis fibers were placed in 13 NHB women [28 (7) years]. 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 N G -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 using 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 following 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 following salsalate, indicating inflammation via NF-κB pathways contributes to impaired cutaneous microvascular function in NHB women.