A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension.

Published

Journal Article

The mechanism by which hypoxia [low partial pressure of O(2) (pO(2))] elicits signaling to regulate pulmonary arterial pressure is incompletely understood. We considered the possibility that, in addition to its effects on smooth muscle, hypoxia may influence pulmonary vascular tone through an effect on RBCs. We report that exposure of native RBCs to sustained hypoxia is accompanied by a buildup of heme iron-nitrosyl (FeNO) species that are deficient in pO(2-)governed intramolecular transfer of NO to cysteine thiol, yielding a deficiency in the vasodilator S-nitrosohemoglobin (SNO-Hb). S-nitrosothiol (SNO)-deficient RBCs produce impaired vasodilator responses in vitro and exaggerated pulmonary vasoconstrictor responses in vivo and are defective in oxygenating the blood. RBCs from hypoxemic patients with elevated pulmonary arterial pressure (PAP) exhibit a similar FeNO/SNO imbalance and are thus deficient in pO(2)-coupled vasoregulation. Chemical restoration of SNO-Hb levels in both animals and patients restores the vasodilator activity of RBCs, and this activity is associated with improved oxygenation and lower PAPs.

Full Text

Duke Authors

Cited Authors

  • McMahon, TJ; Ahearn, GS; Moya, MP; Gow, AJ; Huang, Y-CT; Luchsinger, BP; Nudelman, R; Yan, Y; Krichman, AD; Bashore, TM; Califf, RM; Singel, DJ; Piantadosi, CA; Tapson, VF; Stamler, JS

Published Date

  • October 11, 2005

Published In

Volume / Issue

  • 102 / 41

Start / End Page

  • 14801 - 14806

PubMed ID

  • 16203976

Pubmed Central ID

  • 16203976

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0506957102

Language

  • eng

Conference Location

  • United States