Independent and Cumulative Effects of Superoxide and iNOS on Cutaneous NO‐Dependent Vasodilation in Normotensive Non‐Hispanic Blacks and Whites

Abstract

Cardiovascular disease is the foremost cause of morbidity and mortality in non-Hispanic Blacks (NHB). This may be due, in part, to reduced microvascular endothelial nitric oxide (NO) bioavailability and increased oxidative stress. The purpose of this study was to investigate the role of iNOS and superoxide, individually and cumulatively, in the cutaneous microvascular response to local heating in normotensive NHB and non-Hispanic Whites (NHW). Participants (n = 6 per group) were instrumented with four microdialysis fibers 1) lactated Ringer's solution (control), 2) 0.1 mM 1400W iNOS inhibitor, 3) 10 μM tempol, a superoxide dismutase mimetic to scavenge superoxide, and 4) combined 1400W + tempol. Following perfusate infusion, local skin temperature was increased via rapid local heating to 39°C (0.1°C s-1). Once skin blood flow plateaued, 20 mM L-NAME was infused to quantify endothelial NOS-dependent vasodilation to the local heating response. Following L-NAME infusion, the local heaters were increased to 43°C and 54mM of sodium nitroprusside was infused to elicit maximal cutaneous vasodilation. Skin blood flow was measured via laser-doppler flowmetry (LDF) throughout the local heating protocol. Percent NO contribution (%NO) was calculated as the difference between the local heating plateau and the post-L-NAME plateau multiplied by 100. Data are means ± SD. The %NO contribution was reduced at control sites in NHB relative to NHW (46 ± 5 vs. 62 ± 10 %NO, p = 0.03). Each experimental site was significantly different compared to control in NHB participants [(1400W, 63 ± 7 %NO, p = 0.01); (tempol, 61 ± 8 %NO, p = 0.01); (combined, 77 ± 9 %NO, p < 0.01)]. There was no effect of any of the treatments on %NO in NHW participants. Percent NO contribution at the combined site in NHB was significantly higher compared to control in NHW (p = 0.02). These data indicate combined superoxide scavenging and iNOS inhibition can increase endothelial NO-dependent cutaneous vasodilation more than either treatment alone in NHB.