Hemodynamic Effects of Glutathione-Liganded Binuclear Dinitrosyl Iron Complex: Evidence for Nitroxyl Generation and Modulation by Plasma Albumin

Molecular Pharmacology
Taiming LiuArlin B Blood

Abstract

Glutathione-liganded binuclear dinitrosyl iron complex (glut-BDNIC) has been proposed to be a donor of nitric oxide (NO). This study was undertaken to investigate the mechanisms of vasoactivity, systemic hemodynamic effects, and pharmacokinetics of glut-BDNIC. To test the hypothesis that glut-BDNICs vasodilate by releasing NO in its reduced [nitroxyl (HNO)] state, a bioassay method of isolated, preconstricted ovine mesenteric arterial rings was used in the presence of selective scavengers of HNO or NO free radical (NO•); the vasodilatory effects of glut-BDNIC were found to have characteristics similar to those of an HNO donor and markedly different than an NO• donor. In addition, products of the reaction of glut-BDNIC with CPTIO [2-(4-carboxyphenyl)-4,4,5-tetramethyl imidazoline-1-oxyl-3-oxide] were found to have electron paramagnetic characteristics similar to those of an HNO donor compared with an NO• donor. In contrast to S-nitroso-glutathione, which was vasodilative both in vitro and in vivo, the potency of glut-BDNIC-mediated vasodilation was markedly diminished in both rats and sheep. Wire myography showed that plasma albumin contributed to this loss of hypotensive effects, an effect abolished by modification of the cyste...Continue Reading

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Citations

Mar 3, 2020·The Journal of Physiology·George T MukoseraArlin B Blood
Aug 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Trnka DanielLillig Christopher Horst
Aug 20, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Arlin B BloodGordon G Power
Aug 24, 2020·Free Radical Biology & Medicine·George T MukoseraArlin B Blood
Dec 25, 2019·Nitric Oxide : Biology and Chemistry·Taiming LiuArlin B Blood
May 6, 2021·Cell Biochemistry and Biophysics·Renata Smulik-IzydorczykAdam Sikora
May 18, 2021·Biochemistry. Biokhimii︠a︡·Elvin S AllakhverdievTamila V Martynyuk

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