1. Inhibition of nuclear factor-κB activation improves non-nitric oxide-mediated cutaneous microvascular function in reproductive-aged healthy women.
- Author
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Content, Virginia G., Williams, Auni C., and Alexander, Lacy M.
- Subjects
TRANSCRIPTION factors ,METHYL formate ,ENDOTHELIUM diseases ,SODIUM nitroferricyanide ,MICRODIALYSIS ,NATURAL immunity - Abstract
The transcriptional regulator nuclear factor-κB (NF-κB) is a mediator of endothelial dysfunction. Inhibiting NF-κB with salsalate is used to investigate inflammatory mechanisms contributing to accelerated cardiovascular disease risk. However, in the absence of disease, inhibition of NF-κB can impact redox mechanisms, resulting in paradoxically decreased endothelial function. This study aimed to measure microvascular endothelial function during inhibition of the transcriptional regulator NF-κB in reproductive-aged healthy women. In a randomized, single-blind, crossover, placebo-controlled design, nine healthy women were randomly assigned oral salsalate (1,500 mg, twice daily) or placebo treatments for 5 days. Subjects underwent graded perfusion with the endothelium-dependent agonist acetylcholine (ACh, 10
−10 to 10−1 M, 33°C) alone and in combination with 15 mM NG -nitro- l -arginine methyl ester [ l -NAME; nonselective nitric oxide (NO) synthase inhibitor] through intradermal microdialysis. Laser-Doppler flux was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated as flux divided by mean arterial pressure and normalized to site-specific maximum (CVC%max ; 28 mM sodium nitroprusside + 43°C). The l -NAME sensitive component was calculated as the difference between the areas under the dose-response curves. During the placebo and salsalate treatments, the l -NAME sites were reduced compared with the control sites (both P < 0.0001). Across treatments, there was a significant difference between the control and l -NAME sites, where both sites shifted upward following salsalate treatment (both P < 0.0001), whereas the l -NAME-sensitive component was not different (P = 0.94). These data demonstrate that inhibition of the transcriptional regulator NF-κB improves cutaneous microvascular function in reproductive-aged healthy women through non-NO-dependent mechanisms. NEW & NOTEWORTHY: The transcription factor nuclear factor-κB (NF-κB) regulates multiple aspects of innate and adaptive immunity by encoding for genes that participate in inflammation and impact endothelial function following NF-κB inhibition with salsalate treatment. Our results show that cutaneous microvascular function is increased through non-nitric oxide (NO)-dependent mechanisms following salsalate treatment in reproductive-aged healthy women. [ABSTRACT FROM AUTHOR]- Published
- 2024
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