Endothelin A receptor inhibition increases nitric oxide-dependent vasodilation independent of superoxide in non-Hispanic Black young adults

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 mu M 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 degrees C to 39 degrees 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.

Automated summary

Young non-Hispanic Black adults have reduced microvascular endothelial function compared with non-Hispanic White counterparts. The inhibition of endothelin-1 A receptor (ETAR) contributes to the reduced vasodilation in young non-Hispanic Black adults, independent of superoxide production.