Assessments of the chemistry and vasodilatory activity of nitrite with hemoglobin under physiologically relevant conditions.

Published

Journal Article

Hypoxic vasodilation involves detection of the oxygen content of blood by a sensor, which rapidly transduces this signal into vasodilatory bioactivity. Current perspectives on the molecular mechanism of this function hold that hemoglobin (Hb) operates as both oxygen sensor and a condition-responsive NO reactor that regulates the dispensing of bioactivity through release of the NO group from the beta-cys93 S-nitroso derivative of Hb, SNO-Hb. A common path to the formation of SNO-Hb involves oxidative transfer of the NO-group from heme to thiol. We have previously reported that the reaction of nitrite with deoxy-Hb, which furnishes heme-Fe(II)NO, represents one attractive route for the formation of SNO-Hb. Recent literature, however, posits that the nitrite-reductase reaction of Hb might produce physiological vasodilatory effects through NO that evades trapping on heme-Fe(II) and may be stored before release as Fe(III)NO. In this article, we briefly review current perspectives in NO biology on the nitrite-reductase reaction of Hb. We report in vitro spectroscopic (UV/Vis, EPR) studies that are difficult to reconcile with suggestions that this reaction either generates a heme-Fe(III)NO reservoir or significantly liberates NO. We further show in bioassay experiments that combinations of nitrite and deoxy-Hb--under conditions that suppress SNO-Hb formation--exhibit no direct vasodilatory activity. These results help underscore the differences between physiological, RBC-regulated, hypoxic vasodilation versus pharmacological effects of exogenous nitrite.

Full Text

Duke Authors

Cited Authors

  • Luchsinger, BP; Rich, EN; Yan, Y; Williams, EM; Stamler, JS; Singel, DJ

Published Date

  • April 2005

Published In

Volume / Issue

  • 99 / 4

Start / End Page

  • 912 - 921

PubMed ID

  • 15811508

Pubmed Central ID

  • 15811508

International Standard Serial Number (ISSN)

  • 0162-0134

Digital Object Identifier (DOI)

  • 10.1016/j.jinorgbio.2004.12.010

Language

  • eng

Conference Location

  • United States