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

Publication ,  Journal Article
McMahon, TJ; Ahearn, GS; Moya, MP; Gow, AJ; Huang, Y-CT; Luchsinger, BP; Nudelman, R; Yan, Y; Krichman, AD; Bashore, TM; Califf, RM ...
Published in: Proc Natl Acad Sci U S A
October 11, 2005

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 11, 2005

Volume

102

Issue

41

Start / End Page

14801 / 14806

Location

United States

Related Subject Headings

  • Sus scrofa
  • S-Nitrosothiols
  • Rabbits
  • Pulmonary Gas Exchange
  • Oxygen
  • Nitrogen Oxides
  • Nitrites
  • Nitric Oxide
  • Middle Aged
  • Lung
 

Citation

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McMahon, T. J., Ahearn, G. S., Moya, M. P., Gow, A. J., Huang, Y.-C., Luchsinger, B. P., … Stamler, J. S. (2005). A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A, 102(41), 14801–14806. https://doi.org/10.1073/pnas.0506957102
McMahon, Timothy J., Gregory S. Ahearn, Martin P. Moya, Andrew J. Gow, Yuh-Chin T. Huang, Benjamin P. Luchsinger, Raphael Nudelman, et al. “A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension.Proc Natl Acad Sci U S A 102, no. 41 (October 11, 2005): 14801–6. https://doi.org/10.1073/pnas.0506957102.
McMahon TJ, Ahearn GS, Moya MP, Gow AJ, Huang Y-CT, Luchsinger BP, et al. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14801–6.
McMahon, Timothy J., et al. “A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension.Proc Natl Acad Sci U S A, vol. 102, no. 41, Oct. 2005, pp. 14801–06. Pubmed, doi:10.1073/pnas.0506957102.
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. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14801–14806.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 11, 2005

Volume

102

Issue

41

Start / End Page

14801 / 14806

Location

United States

Related Subject Headings

  • Sus scrofa
  • S-Nitrosothiols
  • Rabbits
  • Pulmonary Gas Exchange
  • Oxygen
  • Nitrogen Oxides
  • Nitrites
  • Nitric Oxide
  • Middle Aged
  • Lung