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Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension.

Publication ,  Conference
Pawloski, JR; McMahon, TJ; Moya, MP; Gow, AJ; Huang, Y-CT; Luchsinger, BJ; Krichman, AD; Bashore, TM; Califf, RM; Singel, DJ; Piantadosi, CA ...
Published in: Blood
November 16, 2004

Recent studies have suggested that binding of oxygen to hemoglobin (Hb) facilitates reactions of nitric oxide (NO) that lead to production of S-nitrosohemoglobin (SNO-Hb), and that vasodilator S-nitrosthiol (SNO) is dispensed by red blood cells (RBCs) at low oxygen tension (pO2) to dilate blood vessels. In human lungs, NO bioactivity serves to attenuate hypoxic pulmonary vasoconstriction (HPV). We therefore considered the possibility that RBC-SNO may oppose HPV and that defective vasodilation by RBCs may contribute to the pathophysiology of pulmonary arterial hypertension (PAH). Here we report that RBCs from patients with PAH exhibit substantial depletion of SNO-Hb and consequent impairment in hypoxia-mediated vasodilation. Furthermore, levels of RBC-NO correlated inversely with pulmonary artery pressures. A SNO-Hb deficiency characteristic of PAH was reproduced in control RBCs by hypoxia: loss of SNO-Hb was accompanied by a buildup of heme-NO species that are deficient in the pO2-governed intramolecular transfer of NO to cysteine thiol, yielding RBCs deficient in NO bioactivity. SNO-deficient RBCs produced exaggerated HPV responses as compared to SNO-replete RBCs. In PAH patients, SNO-Hb repletion fully restored the hypoxic vasodilator activity of RBCs. Our results suggest that a deficiency in RBC-SNO contributes to pulmonary hypertension and hypoxemia, and that repletion of RBC-SNO represents a rational strategy for treating PAH patients.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2004

Volume

104

Issue

11

Start / End Page

1583 / 1583

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
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MLA
NLM
Pawloski, J. R., McMahon, T. J., Moya, M. P., Gow, A. J., Huang, Y.-C., Luchsinger, B. J., … Stamler, J. S. (2004). Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension. In Blood (Vol. 104, pp. 1583–1583). American Society of Hematology. https://doi.org/10.1182/blood.v104.11.1583.1583
Pawloski, John R., Timothy J. McMahon, Martin P. Moya, Andrew J. Gow, Yuh-Chin T. Huang, Benjamin J. Luchsinger, Abigail D. Krichman, et al. “Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension.” In Blood, 104:1583–1583. American Society of Hematology, 2004. https://doi.org/10.1182/blood.v104.11.1583.1583.
Pawloski JR, McMahon TJ, Moya MP, Gow AJ, Huang Y-CT, Luchsinger BJ, et al. Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension. In: Blood. American Society of Hematology; 2004. p. 1583–1583.
Pawloski, John R., et al. “Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension.Blood, vol. 104, no. 11, American Society of Hematology, 2004, pp. 1583–1583. Crossref, doi:10.1182/blood.v104.11.1583.1583.
Pawloski JR, McMahon TJ, Moya MP, Gow AJ, Huang Y-CT, Luchsinger BJ, Krichman AD, Bashore TM, Califf RM, Singel DJ, Piantadosi CA, Tapson VF, Stamler JS. Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension. Blood. American Society of Hematology; 2004. p. 1583–1583.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2004

Volume

104

Issue

11

Start / End Page

1583 / 1583

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology