(A) Following oral 15NO3−, no significant increase in methemoglobin (MetHb) occurs. (B) Following oral 15NO2−, a significant rise in MetHb occurs through 1 hr. (C) A representative EPR spectra (red) shows the characteristic hyperfine splitting of 15NO-Hb from one subject following oral 15NO2− (raw tracings shown in blue). The fit is composed of 42% pentacoordinate 15N alphanitrosyl Hb, 21% hexacoordinate alphanitrosyl Hb, and 38% betanitrosyl Hb. Inclusion of pentacoordinate 14N alphanitrosyl Hb does not substantially improve the fit (Fig. S3B). (D) 15NO-Hb formation is detected with oral 15NO2− treatment only at 0.5 to 1 hours, with no 15NO-Hb detected with oral 15NO3− treatment. NS = not significant, N.D. = not detected. Repeated measures ANOVA with time as the within-subject effect was used to evaluate response to drug treatment for the endpoint measures in A–B.