Endothelial dysfunction is associated with cardiovascular disease development, nitric oxide (NO) deficiencies, and may be limb or sex-specific. Prior in vitro work indicated that the transient receptor potential vanilloid channel-1 (TRPV1) is expressed in human arteries and the TRPV1 agonist capsaicin alters vasodilation in an endothelium-dependent manner; however, it is unknown if this translates in vivo or is limb or sex-dependent. Therefore, we sought to determine if there was limb or sex-specificity in the effect of capsaicin on microvascular function using near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (StO2) reperfusion slope. In a blinded placebo-controlled crossover design, 45 young males (M: n = 25) and females (F: n = 20), the reperfusion slopes of the forearm and quadriceps were assessed, and a urine sample obtained to assay for nitrate/nitrite (NOx) concentrations and antioxidant capacity after acutely ingesting placebo or capsaicin. Under placebo, females had greater reperfusion rates in both the forearm (M: 0.44 ± 0.24 vs. F: 0.98 ± 0.46 %/sec; p = 0.002, d = -1.50) and quadricep (M: 0.86 ± 0.31 vs. F: 1.17 ± 0.43 %/sec; p = 0.010, d = -0.85). Capsaicin decreased microvascular responsiveness in the forearm of females (placebo: 0.98 ± 0.45 vs. capsaicin: 0.84 ± 0.45 %/sec) as compared to males (placebo: 0.45 ± 0.24 vs. capsaicin: 0.38 ± 0.16 %/sec, interaction p < 0.001, η2 = 0.475). There was a sex*treatment interaction for NOx concentrations, where males increased (placebo: 21.13 ± 12.83 vs. capsaicin: 23.82 ± 13.34 μM), while females decreased (placebo: 22.78 ± 14.40 vs. capsaicin: 14.43 ± 10.01 μM; p = 0.037, η2 = 0.042). Using NIRS to assess microvascular function, there is apparent limb and sex-specificity, and, for the first-time, document that acute oral capsaicin alters reperfusion slope in a sexually divergent manner.
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