A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension
| Autor: | Raphael Nudelman, Thomas M. Bashore, Yuh-Chin T. Huang, Timothy J. McMahon, Abigail Krichman, Martin P Moya, Andrew J. Gow, Jonathan S. Stamler, Claude A. Piantadosi, Robert M. Califf, Victor F. Tapson, Yun Yan, Gregory S. Ahearn, Benjamin P. Luchsinger, David J. Singel |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Erythrocytes Hypertension Pulmonary Iron Sus scrofa Vasodilation Blood Pressure Nitric Oxide Nitric oxide chemistry.chemical_compound Hemoglobins Internal medicine medicine Animals Humans Hypoxia Lung Nitrites Multidisciplinary S-Nitrosothiols Chemistry Pulmonary Gas Exchange Hemodynamics S-Nitrosylation Anatomy Hypoxia (medical) Middle Aged Biological Sciences medicine.disease Pulmonary hypertension Oxygen Endocrinology Blood pressure medicine.anatomical_structure Female Nitrogen Oxides Hemoglobin Rabbits medicine.symptom circulatory and respiratory physiology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(41) |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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