Inhibition of iNOS augments cutaneous endothelial NO-dependent vasodilation in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks

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; n = 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 degrees C to 39 degrees C (rate: 0.1 degrees 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%N0 and 28 +/- 5%NO, respectively) relative to normotensive Whites (73 +/- 8%NO; P < 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; P < 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. NEW & NOTEWORTHY 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.

Automated summary

Our study found that inducible nitric oxide synthase (iNOS) plays a role in the reduced nitric oxide (NO)-dependent vasodilation in prehypertensive individuals and Black participants. Inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.