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

91 Цитирования (Scopus)

Выдержка

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

Отпечаток

S-Nitrosothiols
Cell Hypoxia
Pulmonary Hypertension
Nitric Oxide
Erythrocytes
Vasodilator Agents
Lung
Arterial Pressure
Pressure
Partial Pressure
Vasoconstrictor Agents
Heme
Sulfhydryl Compounds
Cysteine
Smooth Muscle
Blood Vessels
S-nitrosohemoglobin
Hypoxia

ASJC Scopus subject areas

  • Genetics
  • General

Цитировать

A nitric oxide processing defect of red blood cells created by hypoxia : Deficiency of S-nitrosohemoglobin in pulmonary hypertension. / McMahon, Timothy J.; Ahearn, Gregory S.; Moya, Martin P.; Gow, Andrew J.; Huang, Yuh Chin T; Luchsinger, Benjamin P.; Nudelman, Raphael; Yan, Yun; Krichman, Abigail D.; Bashore, Thomas M.; Califf, Robert M.; Singel, David J.; Piantadosi, Claude A.; Tapson, Victor F.; Stamler, Jonathan S.

В: Proceedings of the National Academy of Sciences of the United States of America, Том 102, № 41, 11.10.2005, стр. 14801-14806.

Результат исследований: Материалы для журналаСтатья

McMahon, TJ, Ahearn, GS, Moya, MP, Gow, AJ, Huang, YCT, Luchsinger, BP, Nudelman, R, Yan, Y, Krichman, AD, Bashore, TM, Califf, RM, Singel, DJ, Piantadosi, CA, Tapson, VF & Stamler, JS 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, том. 102, № 41, стр. 14801-14806. https://doi.org/10.1073/pnas.0506957102
McMahon, Timothy J. ; Ahearn, Gregory S. ; Moya, Martin P. ; Gow, Andrew J. ; Huang, Yuh Chin T ; Luchsinger, Benjamin P. ; Nudelman, Raphael ; Yan, Yun ; Krichman, Abigail D. ; Bashore, Thomas M. ; Califf, Robert M. ; Singel, David J. ; Piantadosi, Claude A. ; Tapson, Victor F. ; Stamler, Jonathan S. / A nitric oxide processing defect of red blood cells created by hypoxia : Deficiency of S-nitrosohemoglobin in pulmonary hypertension. В: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Том 102, № 41. стр. 14801-14806.
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abstract = "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.",
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T1 - A nitric oxide processing defect of red blood cells created by hypoxia

T2 - Deficiency of S-nitrosohemoglobin in pulmonary hypertension

AU - McMahon, Timothy J.

AU - Ahearn, Gregory S.

AU - Moya, Martin P.

AU - Gow, Andrew J.

AU - Huang, Yuh Chin T

AU - Luchsinger, Benjamin P.

AU - Nudelman, Raphael

AU - Yan, Yun

AU - Krichman, Abigail D.

AU - Bashore, Thomas M.

AU - Califf, Robert M.

AU - Singel, David J.

AU - Piantadosi, Claude A.

AU - Tapson, Victor F.

AU - Stamler, Jonathan S.

PY - 2005/10/11

Y1 - 2005/10/11

N2 - 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.

AB - 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.

KW - Hemoglobin

KW - Red blood cell vasodilation

KW - S-nitrosylation

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