Endothelin A receptor inhibition increases nitric oxide-dependent vasodilation independent of superoxide in non-Hispanic Black young adults.
Endothelin A receptor inhibition increases nitric oxide-dependent vasodilation independent of superoxide in non-Hispanic Black young adults.
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DOI：
10.1152/japplphysiol.00739.2022
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发表时间：
2023-04-01
影响因子：
3.3
通讯作者：
Wong, Brett J.
中科院分区：
文献类型：
--
作者：
Turner, Casey G.;Hayat, Matthew J.;Grosch, Caroline;Quyyumi, Arshed A.;Otis, Jeffrey S.;Wong, Brett J.
与非西班牙裔白色人相比，年轻的非西班牙裔黑人成年人的微血管内皮功能降低，但其机制尚未完全阐明。本研究的目的是探讨内皮素-1 A受体（ETAR）和超氧化物对皮肤微血管功能的影响，在年轻的非西班牙裔黑人（n = 10）和白色（n = 10）成人。参与者使用四种皮内微透析纤维：1）乳酸林格氏液（对照），2）500 nM BQ-123（ETAR拮抗剂），3）10 μM tempol（超氧化物歧化酶模拟物）和4）BQ-123 + tempol。通过激光多普勒血流仪（LDF）评估皮肤血流，并将每个部位从33°C快速局部加热至39°C。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]以定量NO依赖性血管舒张。数据为平均值±标准差。与非西班牙裔白色年轻人相比，非西班牙裔黑人的NO依赖性血管舒张功能降低（P < 0.01）。与对照组（53 ± 13%NO，P = 0.01）相比，非西班牙裔黑人年轻人中BQ-123位点（73 ± 10%NO）和BQ-123 + tempol位点（71 ± 10%NO）的NO依赖性血管舒张增加。Tempol单独对非西班牙裔黑人青年的NO依赖性血管舒张没有影响（63 ± 14%NO，P = 0.18）。非西班牙裔黑人和白色年轻成人（80 ± 7%NO）在BQ-123位点的NO依赖性血管舒张无统计学差异（P = 0.15）。ETAR有助于减少NO依赖性血管舒张在非西班牙裔黑人年轻人独立的超氧化物，这表明NO的合成，而不是通过超氧化物NO清除更大的影响。新&值得注意的是，内皮素-1A受体（ETAR）已被证明可以独立地并通过增加超氧化物的产生来降低内皮功能。我们发现，独立的ETAR抑制增加微血管内皮功能在非西班牙裔黑人年轻人。然而，单用超氧化物歧化酶模拟物和与ETAR抑制剂联合给药对微血管内皮功能没有影响，这表明在皮肤微血管中，ETAR对非西班牙裔黑人年轻人的负面影响与超氧化物的产生无关。
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 (ETAR) and superoxide on cutaneous microvascular function in young non-Hispanic Black (n = 10) and White (n = 10) adults. Participants were instrumented with four intradermal microdialysis fibers: 1) lactated Ringer’s (control), 2) 500 nM BQ-123 (ETAR antagonist), 3) 10 μM tempol (superoxide dismutase mimetic), and 4) 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 (P < 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, P = 0.01). Tempol alone had no effect on NO-dependent vasodilation in non-Hispanic Black young adults (63 ± 14%NO, P = 0.18). NO-dependent vasodilation at BQ-123 sites was not statistically different between non-Hispanic Black and White (80 ± 7%NO) young adults (P = 0.15). ETAR 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. NEW & NOTEWORTHY Endothelin-1 A receptors (ETARs) have been shown to reduce endothelial function independently and through increased production of superoxide. We show that independent ETAR inhibition increases microvascular endothelial function in non-Hispanic Black young adults. However, administration of a superoxide dismutase mimetic alone and in combination with ETAR inhibition had no effect on microvascular endothelial function suggesting that, in the cutaneous microvasculature, the negative effects of ETAR in non-Hispanic Black young adults are independent of superoxide production.
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年轻，非西班牙裔黑人男女表现出不同的外围和脑血管反应性。
影响因子：
2.7
作者：
Akins JD;Martin ZT;Patik JC;Curtis BM;Campbell JC;Olvera G;Brothers RM
通讯作者：
Brothers RM
影响因子：
37.8
作者：
Campia, U;Cardillo, C;Panza, JA
通讯作者：
Panza, JA
DOI：
10.1152/ajpheart.00784.2014
发表时间：
2015-03-01
影响因子：
4.8
作者：
Deo, Shekhar H.;Holwerda, Seth W.;Fadel, Paul J.
通讯作者：
Fadel, Paul J.
影响因子：
2.7
作者：
Fieger, Sarah M.;Wong, Brett J.
通讯作者：
Wong, Brett J.
影响因子：
8.3
作者：
Cardillo, C;Kilcoyne, CM;Panza, JA
通讯作者：
Panza, JA