PURPOSE: Non-Hispanic Black (NHB) men and women demonstrate impaired microvascular function compared to their non-Hispanic White counterparts. Microvascular dysfunction in NHB men is primarily driven by increased production of oxidative species through NADPH and xanthine oxidases, whereas in NHB women, inflammatory processes appear to contribute to this dysfunction. However, this is evidenced only indirectly by elevated C-reactive protein and interleukin 6 expression; the direct role of this upregulated systemic inflammation on microvascular dysfunction has not been investigated in vivo in NHB women. We hypothesized that microvascular endothelial function, characterized by nitric oxide (NO)-mediated vasodilation, would increase following a five-day anti-inflammatory oral salsalate; nuclear factor kappa B (NF-κB) activation inhibitor treatment. METHODS: In a randomized, single-blind, placebo-controlled design, oral salsalate (1500mg, b.i.d., 5 days) was used to assess the impact of systemic inflammation on cutaneous microvascular endothelial function in NHB women. Two intradermal microdialysis fibers were placed into the dermal layer of the ventral aspect of the forearm in eleven NHB women Mean (SD): 29 (8) yrs. Laser-Doppler flowmeter probes were placed in local heating units set to 33°C atop the microdialysis sites and red blood cell flux was continuously measured. Increasing concentrations of acetylcholine (ACh; endothelium-dependent vasodilator dissolved in lactated Ringer’s) from 10-10 to 10-1 M were perfused sequentially for 5 min each alone (Control site, CTL) and with 15 mM NG-nitro-L-arginine methyl ester (L-NAME site; NO synthase inhibitor). Following the progressive ACh protocol, 28 mM sodium nitroprusside was perfused and local skin temperature was increased to 43°C to induce maximal cutaneous vasodilation. Cutaneous vascular conductance (CVC) was calculated as the quotient of red blood cell flux over mean arterial pressure and normalized as a percentage of the site-specific maximum (CVC%max). CVC%max data were analyzed using a two-way repeated-measures ANOVA (treatment*site) with corrections for multiple comparisons. RESULTS: Systemic salsalate treatment did not impact the overall magnitude of ACh-induced vasodilation (main effect of treatment, p=0.42), but there was a main effect of site (p=0.0005). L-NAME was not different from CTL in the placebo condition (p=0.26), but L-NAME attenuated ACh-induced vasodilation compared to the CTL site in the salsalate condition (p=0.0001). CONCLUSION: Five days of oral salsalate did not alter the overall magnitude of ACh-induced vasodilation in the skin of otherwise healthy NHB women, but the downstream endothelial mediators contributing to vasodilation were impacted by salsalate with a greater reliance on NO. The data suggest that systemic inflammation limits endothelial NO-mediated vasodilation, but other mechanisms contribute to microvascular dysfunction in NHB women. Supported by Diversity Supplement R01 HL161000-02S2 (VGC), NIH F31 HL170616-01 (ACW), NIH Grant R01 HL161000 (LMA). This abstract was presented at the American Physiology Summit 2026 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.
Content et al. (Fri,) studied this question.