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Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin.

Publication ,  Journal Article
McMahon, TJ; Doctor, A
Published in: Proc Am Thorac Soc
April 2006

Early applications of inhaled nitric oxide (iNO), typically in the treatment of diseases marked by acute pulmonary hypertension, were met by great enthusiasm regarding the purported specificity of iNO: vasodilation by iNO was specific to the lung (without a change in systemic vascular resistance), and within the lung, NO activity was said to be confined spatially and temporally by Hb within the vascular lumen. Underlying these claims were classical views of NO as a short-lived paracrine hormone that acts largely through the heme groups of soluble guanylate cyclase, and whose potential activity is terminated on encountering the hemes of red blood cell (RBC) Hb. These classical views are yielding to a broader paradigm, in which NO-related signaling is achieved through redox-related NO adducts that endow NO synthase products with the ability to act at a distance in space and time from NO synthase itself. Evidence supporting the biological importance of such stable NO adducts is probably strongest for S-nitrosothiols (SNOs), in which NO binds to critical cysteine residues in proteins or peptides. The circulating RBC is a major SNO reservoir, and RBC Hb releases SNO-related bioactivity peripherally on O2 desaturation. These new paradigms describing NO transport also provide a plausible mechanistic understanding of the increasingly recognized peripheral effects of inhaled NO. An explanation for the peripheral actions of inhaled NO is discussed here, and the rationale and results of attempts to exploit the "NO delivery" function of the RBC are reviewed.

Duke Scholars

Published In

Proc Am Thorac Soc

DOI

ISSN

1546-3222

Publication Date

April 2006

Volume

3

Issue

2

Start / End Page

153 / 160

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Vasodilation
  • Respiratory System
  • Nitric Oxide
  • Humans
  • Hemoglobins
  • Erythrocytes
  • Blood Circulation
  • Animals
  • Administration, Inhalation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McMahon, T. J., & Doctor, A. (2006). Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proc Am Thorac Soc, 3(2), 153–160. https://doi.org/10.1513/pats.200507-066BG
McMahon, Timothy J., and Allan Doctor. “Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin.Proc Am Thorac Soc 3, no. 2 (April 2006): 153–60. https://doi.org/10.1513/pats.200507-066BG.
McMahon, Timothy J., and Allan Doctor. “Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin.Proc Am Thorac Soc, vol. 3, no. 2, Apr. 2006, pp. 153–60. Pubmed, doi:10.1513/pats.200507-066BG.

Published In

Proc Am Thorac Soc

DOI

ISSN

1546-3222

Publication Date

April 2006

Volume

3

Issue

2

Start / End Page

153 / 160

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Vasodilation
  • Respiratory System
  • Nitric Oxide
  • Humans
  • Hemoglobins
  • Erythrocytes
  • Blood Circulation
  • Animals
  • Administration, Inhalation