Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia, United States.
Department of Population Health Sciences, School of Public Health, Georgia State University, Atlanta, Georgia, United States.
J Appl Physiol (1985). 2023 Apr 1;134(4):891-899. doi: 10.1152/japplphysiol.00739.2022. Epub 2023 Mar 9.
Young non-Hispanic Black adults have reduced microvascular endothelial function compared with non-Hispanic White counterparts, but the mechanisms are not fully elucidated. The purpose of this study was to investigate the effect of endothelin-1 A receptor (ETR) and superoxide on cutaneous microvascular function in young non-Hispanic Black ( = 10) and White ( = 10) adults. Participants were instrumented with four intradermal microdialysis fibers: ) lactated Ringer's (control), ) 500 nM BQ-123 (ETR antagonist), ) 10 μM tempol (superoxide dismutase mimetic), and ) BQ-123 + tempol. Skin blood flow was assessed via laser-Doppler flowmetry (LDF), and each site underwent rapid local heating from 33°C to 39°C. At the plateau of local heating, 20 mM l-NAME [nitric oxide (NO) synthase inhibitor] was infused to quantify NO-dependent vasodilation. Data are means ± standard deviation. NO-dependent vasodilation was decreased in non-Hispanic Black compared with non-Hispanic White young adults ( < 0.01). NO-dependent vasodilation was increased at BQ-123 sites (73 ± 10% NO) and at BQ-123 + tempol sites (71 ± 10%NO) in non-Hispanic Black young adults compared with control (53 ± 13%NO, = 0.01). Tempol alone had no effect on NO-dependent vasodilation in non-Hispanic Black young adults (63 ± 14%NO, = 0.18). NO-dependent vasodilation at BQ-123 sites was not statistically different between non-Hispanic Black and White (80 ± 7%NO) young adults ( = 0.15). ETR contributes to reduced NO-dependent vasodilation in non-Hispanic Black young adults independent of superoxide, suggesting a greater effect on NO synthesis rather than NO scavenging via superoxide. Endothelin-1 A receptors (ETRs) have been shown to reduce endothelial function independently and through increased production of superoxide. We show that independent ETR inhibition increases microvascular endothelial function in non-Hispanic Black young adults. However, administration of a superoxide dismutase mimetic alone and in combination with ETR inhibition had no effect on microvascular endothelial function suggesting that, in the cutaneous microvasculature, the negative effects of ETR in non-Hispanic Black young adults are independent of superoxide production.
年轻的非西班牙裔黑人成年人的微血管内皮功能比非西班牙裔白人成年人差，但具体机制尚不清楚。本研究的目的是探讨内皮素-1A 受体（ETR）和超氧对年轻的非西班牙裔黑人（n = 10）和白人（n = 10）成年人皮肤微血管功能的影响。研究参与者的四个真皮内微透析纤维上都有仪器：）乳酸林格氏液（对照）、）500 nM BQ-123（ETR 拮抗剂）、）10 μM 替普（超氧化物歧化酶模拟物）和）BQ-123 + 替普。通过激光多普勒血流仪（LDF）评估皮肤血流，每个部位都经历了从 33°C 到 39°C 的快速局部加热。在局部加热的平台期，输注 20 mM l-NAME[一氧化氮（NO）合酶抑制剂]以量化 NO 依赖性血管舒张。数据为平均值±标准差。与非西班牙裔白人年轻人相比，非西班牙裔黑人年轻人的 NO 依赖性血管舒张减少（<0.01）。与对照相比（53±13%NO，n = 0.01），BQ-123 部位（73±10%NO）和 BQ-123+替普部位（71±10%NO）的 NO 依赖性血管舒张增加，非西班牙裔黑人年轻人（n = 0.01）。替普单独对非西班牙裔黑人年轻人的 NO 依赖性血管舒张没有影响（63±14%NO，n = 0.18）。BQ-123 部位的非西班牙裔黑人年轻人和白人年轻人之间的 NO 依赖性血管舒张无统计学差异（80±7%NO，n = 0.15）。内皮素-1A 受体（ETRs）已被证明可独立于超氧化物减少 NO 依赖性血管舒张，这表明它们对 NO 合成的影响大于通过超氧化物的 NO 清除。我们显示，独立的 ETR 抑制可增加非西班牙裔黑人年轻人的微血管内皮功能。然而，单独使用超氧化物歧化酶模拟物以及与 ETR 抑制联合使用对微血管内皮功能均无影响，这表明在皮肤微血管中，非西班牙裔黑人年轻人中 ETR 的负性作用独立于超氧化物的产生。
