Williams Auni C, Content Virginia G, Alexander Lacy M
Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, United States.
Center for Healthy Aging, The Pennsylvania State University, University Park, Pennsylvania, United States.
Am J Physiol Heart Circ Physiol. 2025 Apr 1;328(4):H915-H922. doi: 10.1152/ajpheart.00012.2025. Epub 2025 Mar 6.
Women with endometriosis, an inflammatory disease, are at increased risk of cardiovascular disease and demonstrate impaired microvascular endothelial function, characterized by reduced nitric oxide (NO)-mediated vasodilation. In some clinical cohorts, nuclear factor-kappa B (NFκB) inhibition with salsalate improves endothelial function. We hypothesized that salsalate would improve cutaneous microvascular endothelial function in women with endometriosis. Following placebo or salsalate (3,000 mg·day for 5 days), four intradermal microdialysis probes were placed in 11 women (33 ± 7 yr) with endometriosis. Local heating units (set to 33°C) and laser-Doppler flowmetry (red blood cell flux) probes were placed over the probes. Increasing doses of acetylcholine (ACh; dissolved in lactated Ringer's solution) were perfused, alone (control) or coperfused with: -nitro-l-arginine methyl ester (l-NAME), atorvastatin (statin), or l-NAME + statin (combo). Maximal vasodilation was then induced (local heat at 43°C + sodium nitroprusside perfusion). Data were normalized as percentage of maximal cutaneous vascular conductance (CVC red blood cell flux/mean arterial pressure). To measure macrovascular endothelial function, flow-mediated dilation (FMD) was additionally performed. During placebo, coperfusion with statin did not impact the CVC ACh dose-response ( = 0.93). Oral salsalate attenuated the CVC response to ACh perfusion alone ( < 0.01) but did not impact the l-NAME site ( = 0.09). Salsalate significantly augmented the CVC response of the statin site ( < 0.01) but did not affect the combo site response ( = 1.00). FMD was not different between treatments ( = 0.79). Salsalate treatment impairs vasodilation in the cutaneous microcirculation in women with endometriosis through non-NO-dependent mechanisms. Our results show that oral salsalate treatment negatively impacts microvascular function but does not alter macrovascular function. In contrast to the majority of other clinical populations with endothelial dysfunction, salsalate treatment reduces microcirculatory function through non-NO-dependent mechanisms in women with endometriosis.
患有子宫内膜异位症（一种炎症性疾病）的女性患心血管疾病的风险增加，并且表现出微血管内皮功能受损，其特征是一氧化氮（NO）介导的血管舒张功能降低。在一些临床队列中，使用柳氮磺吡啶抑制核因子-κB（NFκB）可改善内皮功能。我们假设柳氮磺吡啶可以改善子宫内膜异位症女性的皮肤微血管内皮功能。在给予安慰剂或柳氮磺吡啶（3000毫克·天，共5天）后，在11名患有子宫内膜异位症的女性（33±7岁）身上放置了4个皮内微透析探针。在探针上方放置局部加热装置（设定为33°C）和激光多普勒血流仪（红细胞通量）探头。单独灌注递增剂量的乙酰胆碱（ACh；溶解于乳酸林格氏液中），或与以下物质共同灌注：L-硝基精氨酸甲酯（L-NAME）、阿托伐他汀（他汀类药物）或L-NAME+他汀类药物（联合用药）。然后诱导最大血管舒张（43°C局部加热+硝普钠灌注）。数据以最大皮肤血管传导率（CVC红细胞通量/平均动脉压）的百分比进行标准化。为了测量大血管内皮功能，还进行了血流介导的血管舒张（FMD）检测。在使用安慰剂期间，与他汀类药物共同灌注不影响CVC对ACh的剂量反应（P=0.93）。口服柳氮磺吡啶减弱了CVC对单独ACh灌注的反应（P<0.01），但不影响L-NAME部位的反应（P=0.09）。柳氮磺吡啶显著增强了他汀类药物部位的CVC反应（P<0.01），但不影响联合用药部位的反应（P=1.00）。各治疗组之间的FMD无差异（P=0.79）。柳氮磺吡啶治疗通过非NO依赖机制损害子宫内膜异位症女性皮肤微循环中的血管舒张。我们的结果表明，柳氮磺吡啶治疗对微血管功能有负面影响，但不改变大血管功能。与大多数其他内皮功能障碍的临床人群不同，柳氮磺吡啶治疗通过非NO依赖机制降低子宫内膜异位症女性的微循环功能。
