The potential of Angeli's salt to decrease nitric oxide scavenging by plasma hemoglobin (original) (raw)

Angeli’s Salt Counteracts the Vasoactive Effects of Elevated Plasma Hemoglobin

Free Radical Biology and Medicine, 2012

Plasma hemoglobin (Hb) released during intravascular hemolysis has been associated with numerous deleterious effects that may stem from increased nitric oxide (NO) scavenging, but has also been associated with reactive oxygen species generation and platelet activation. Therapies that convert plasma oxyHb to metHb, or metHb to iron-nitrosyl Hb, could be beneficial because these species do not scavenge NO. In this study, we investigated the effects of Angeli's Salt (AS, sodium α-oxyhyponitrite, Na 2 N 2 O 3), a nitroxyl (HNO) and nitrite (NO 2 −) donor, on plasma Hb oxidation and formation of iron-nitrosyl Hb from metHb, and on the vasoactivity of plasma Hb. We hypothesized that AS could ameliorate hemolysis-associated pathology via its preferential reactivity with plasma Hb, as opposed to red cell encapsulated Hb, and through its intrinsic vasodilatory activity. To test this hypothesis, we infused (n=3 per group) (1) cell-free Hb and AS, (2) cell-free Hb + 0.9% NaCl, (3) AS + 3% Albumin, and (4) 3% Albumin + 0.9% NaCl (colloid controls for Hb and AS, respectively) in a canine model. Co-infusion of AS and cell-free Hb led to preferential conversion of plasma Hb to metHb, but the extent of conversion was lower than anticipated based on the in vivo concentration of AS relative to plasma Hb. This lower metHb yield was likely due to reactions of nitroxyl-derived AS with plasma components such as thiol-* Drs. Solomon and Bellavia share first authorship.