Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia.
School of Public Health, Georgia State University, Atlanta, Georgia.
Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H190-H199. doi: 10.1152/ajpheart.00644.2020. Epub 2020 Oct 30.
We tested the hypothesis that inducible nitric oxide synthase (iNOS) contributes to reduced nitric oxide (NO)-dependent vasodilation in non-Hispanic Blacks and prehypertensive non-Hispanic Whites. Twenty Black and twenty White participants (10 normotensive, 10 prehypertensive per group; = 40 total) participated in this study. Participants were instrumented with two microdialysis fibers, and each site was randomized as control (lactated Ringer) or iNOS inhibition (0.1 mM 1400W). Laser-Doppler flow probes and local heaters were used to measure skin blood flow and heat the skin to induce vasodilation, respectively. Each site was heated from 33°C to 39°C (rate: 0.1°C/s). Once a plateau was established, 20 mM nitro-l-arginine methyl ester (l-NAME), a nonspecific NOS inhibitor, was infused at each site to quantify NO-dependent vasodilation. At control sites, %NO-dependent vasodilation was reduced in prehypertensive Whites (47 ± 10%NO) and in both normotensive and prehypertensive Blacks (39 ± 9%NO and 28 ± 5%NO, respectively) relative to normotensive Whites (73 ± 8%NO; < 0.0001 for all comparisons). Compared with respective control sites, iNOS inhibition increased NO-dependent vasodilation in prehypertensive Whites (68 ± 8%NO) and in both normotensive and prehypertensive Blacks (78 ± 8%NO and 55 ± 6%NO, respectively; < 0.0001 for all comparisons). We failed to find an effect for normotensive Whites (77 ± 7%NO). After iNOS inhibition, %NO-dependent vasodilation was similar between normotensive Whites, prehypertensive Whites, and normotensive Blacks. Inhibition of iNOS increased NO-dependent vasodilation to a lesser extent in prehypertensive Blacks. These data suggest that iNOS contributes to reduced NO-dependent vasodilation in prehypertension and in Black participants. Inducible nitric oxide synthase (iNOS) is typically upregulated in conditions of increased oxidative stress and may have detrimental effects on the vasculature. Endothelial nitric oxide (NO), which is cardioprotective, is reduced in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks. We found that inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.Inducible nitric oxide (NO) synthase (iNOS) can be upregulated under conditions of increased oxidative stress and may have detrimental effects on the vasculature. Endothelial NO, which is cardioprotective, is reduced in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks. We found that inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.
我们检验了这样一个假设，即在非裔美国人和非裔高血压前期白种人中，诱导型一氧化氮合酶（iNOS）会导致一氧化氮（NO）依赖性血管舒张减少。二十名黑人和二十名白人参与者（每组 10 名正常血压，10 名高血压前期；总共 40 名）参加了这项研究。参与者被安置了两个微透析纤维，每个部位随机作为对照（乳酸林格氏液）或 iNOS 抑制（0.1mM 1400W）。激光多普勒血流探针和局部加热器用于分别测量皮肤血流和加热皮肤以诱导血管舒张。每个部位从 33°C 加热到 39°C（速率：0.1°C/s）。一旦达到稳定状态，每个部位都注入 20mM 硝基-L-精氨酸甲酯（l-NAME），一种非特异性 NOS 抑制剂，以量化 NO 依赖性血管舒张。在对照部位，高血压前期白种人（47±10%NO）和正常血压及高血压前期黑人（39±9%NO 和 28±5%NO）的 NO 依赖性血管舒张均低于正常血压白种人（73±8%NO；所有比较均<0.0001）。与各自的对照部位相比，iNOS 抑制增加了高血压前期白种人（68±8%NO）和正常血压及高血压前期黑人（78±8%NO 和 55±6%NO）的 NO 依赖性血管舒张；所有比较均<0.0001）。我们没有发现正常血压白种人（77±7%NO）有这种作用。在 iNOS 抑制后，正常血压白种人、高血压前期白种人和正常血压黑人之间的 NO 依赖性血管舒张相似。iNOS 抑制对高血压前期黑人的 NO 依赖性血管舒张的影响较小。这些数据表明，iNOS 导致高血压前期和黑人参与者的 NO 依赖性血管舒张减少。诱导型一氧化氮合酶（iNOS）通常在氧化应激增加的情况下上调，可能对血管系统产生有害影响。内皮一氧化氮（NO）具有心脏保护作用，在非裔高血压前期白人和非裔黑人群体中减少。我们发现，抑制 iNOS 可以增加高血压前期白种人和正常血压及高血压前期黑种人参与者的内皮型一氧化氮（NO）依赖性血管舒张。诱导型一氧化氮合酶（iNOS）可在氧化应激增加的情况下上调，可能对血管系统产生有害影响。具有心脏保护作用的内皮一氧化氮（NO）在非裔高血压前期白人和非裔黑人群体中减少。我们发现，抑制 iNOS 可以增加高血压前期白种人和正常血压及高血压前期黑种人参与者的内皮型一氧化氮（NO）依赖性血管舒张。
