SNO-hemoglobin and hypoxic vasodilation (original) (raw)

Nature Medicine volume 14, pages 1008–1009 (2008)Cite this article

To the Editor:

In a recent Letter in Nature Medicine, Isbell et al.1 state that _S_-nitrosohemoglobin (SNO-Hb) is not essential for hypoxic vasodilation on the basis of observations in mice in which both the α- and β-chains of hemoglobin had been replaced with the human versions, with or without mutation of the Cys93 residue of the β-chain (βCys93) to alanine. More specifically, the authors indicate that βCys93 mutation “resulted in no deficits in systemic or pulmonary hemodynamics.”1 As evidence, they report that systemic and pulmonary arterial blood pressures under basal conditions and “time to fatigue” during strenuous exercise did not differ between humanized mice and humanized, βCys93-mutant mice. However, neither blood pressure nor time to fatigue has any bearing on hypoxic vasodilation or on any of the proposed functions of SNO-Hb. Moreover, blood pressure does not constitute a meaningful assessment of systemic or pulmonary hemodynamics. Additionally, the authors overlooked a major defect in the vasorelaxation evoked by humanized mouse red blood cells (RBCs) in vitro and also discounted changes in the βCys93-mutant mice that strongly suggest defective tissue oxygenation, namely increased concentrations of hemoglobin and bioactive low-mass _S_-nitrosothiols1. These changes are the expected physiological correlates of impaired hypoxic vasodilation.

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, 27710, North Carolina, USA
    Jonathan S Stamler & Claude A Piantadosi
  2. Department of Biochemistry, Duke University Medical Center, Durham, 27710, North Carolina, USA
    Jonathan S Stamler
  3. Department of Chemistry and Biochemistry, Montana State University, Bozeman, 59717, Montana, USA
    David J Singel

Authors

  1. Jonathan S Stamler
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  2. David J Singel
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  3. Claude A Piantadosi
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Stamler, J., Singel, D. & Piantadosi, C. SNO-hemoglobin and hypoxic vasodilation.Nat Med 14, 1008–1009 (2008). https://doi.org/10.1038/nm1008-1008

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