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

Timothy J. McMahon, Gregory S. Ahearn, Martin P. Moya, Andrew J. Gow, Yuh Chin T Huang, Benjamin P. Luchsinger, Raphael Nudelman, Yun Yan, Abigail D. Krichman, Thomas M. Bashore, Robert M. Califf, David J. Singel, Claude A. Piantadosi, Victor F. Tapson, Jonathan S. Stamler

Результат исследований: Материалы для журналаСтатья

95 Цитирования (Scopus)

Аннотация

The mechanism by which hypoxia [low partial pressure of O2 (pO2)] 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 pO2-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 pO2-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.

Язык оригиналаАнглийский
Страницы (с-по)14801-14806
Число страниц6
ЖурналProceedings of the National Academy of Sciences of the United States of America
Том102
Номер выпуска41
DOI
СостояниеОпубликовано - 11 окт 2005
Опубликовано для внешнего пользованияДа

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ASJC Scopus subject areas

  • Genetics
  • General

Цитировать

McMahon, T. J., Ahearn, G. S., Moya, M. P., Gow, A. J., Huang, Y. C. T., Luchsinger, B. P., Nudelman, R., Yan, Y., Krichman, A. D., Bashore, T. M., Califf, R. M., Singel, D. J., Piantadosi, C. A., Tapson, V. F., & Stamler, J. S. (2005). A nitric oxide processing defect of red blood cells created by hypoxia: Deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proceedings of the National Academy of Sciences of the United States of America, 102(41), 14801-14806. https://doi.org/10.1073/pnas.0506957102