Effect of iNOS on Cutaneous Thermal Hyperemia in Non‐Hispanic Blacks versus Non‐Hispanic Whites

Abstract

Non‐Hispanic Blacks exhibit a blunted cutaneous microvascular response to local heating due, in part, to a decrease in nitric oxide (NO) bioavailability compared to non‐Hispanic Whites. Inducible NO synthase (iNOS) is known to contribute to vascular dysfunction; however, it is unknown whether iNOS contributes to microvascular dysfunction in NHB. The purpose of this study was to examine the role of iNOS on cutaneous microvascular function in NHB vs. NHW. Young, healthy non‐Hispanic Black and White participants (n = 4 per group) were instrumented with 2 microdialysis fibers for infusion of lactated Ringer's solution (control) and 0.1 mM 1400W (iNOS inhibitor), respectively. Following Ringer's and 1400W infusion, local skin temperature was increased via rapid local heating to 39°C at a rate of 0.1°C s−1. Once skin blood flow plateaued, 20 mM L‐NAME was infused to quantify endothelial NO synthase (eNOS)‐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 endothelium‐independent cutaneous vasodilation. Skin blood flow was measured via laser‐doppler flowmetry (LDF) throughout the local heating protocol. Cutaneous vascular conductance (CVC) was calculated as LDF flow divided by mean arterial pressure and normalized to maximum (%CVCmax). iNOS inhibition minimally increased the initial peak in non‐Hispanic Blacks (33±6 vs. 41±8 %CVCmax) but had no effect in non‐Hispanic Whites (53±9 vs. 55±6 %CVCmax), suggesting an increased sensory nerve response in non‐Hispanic Blacks following blockade. Inhibition of iNOS (66±10 %CVCmax) did not alter microvascular function compared to control (70±14 %CVCmax) in non‐Hispanic Whites; however, microvascular function increased (47±11 vs. 60±10 %CVCmax) in non‐Hispanic Blacks, suggesting an increase in basal iNOS concentrations. Notably, iNOS inhibition in non‐Hispanic Blacks increased %CVCmax to a level similar to non‐Hispanic Whites. The %NO‐dependent vasodilation did not change in non‐Hispanic Whites with infusion of 1400W (60±5 vs. 61±5 %); however, infusion of 1400W increased the %NO‐dependent vasodilation in non‐Hispanic Blacks (44±6 vs. 57±3 %), suggesting increased levels of circulating iNOS impairs endothelial‐dependent vasodilation. These findings indicate iNOS‐derived NO contributes to reduced eNOS‐dependent microvascular vasodilation in young, healthy non‐Hispanic Blacks.Support or Funding InformationGrant Number: 1R01HL141205‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.