Document Detail


Oxygen regulation of tumor perfusion by S-nitrosohemoglobin reveals a pressor activity of nitric oxide.
MedLine Citation:
PMID:  15879309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In erythrocytes, S-nitrosohemoglobin (SNO-Hb) arises from S-nitrosylation of oxygenated hemoglobin (Hb). It has been shown that SNO-Hb behaves as a nitric oxide (NO) donor at low oxygen tensions. This property, in combination with oxygen transport capacity, suggests that SNO-Hb may have unique potential to reoxygenate hypoxic tissues. The present study was designed to test the idea that the allosteric properties of SNO-Hb could be manipulated to enhance oxygen delivery in a hypoxic tumor. Using Laser Doppler flowmetry, we showed that SNO-Hb infusion to animals breathing 21% O2 reduced tumor perfusion without affecting blood pressure and heart rate. Raising the pO2 (100% O2) slowed the release of NO bioactivity from SNO-Hb (ie, prolonged the plasma half-life of the SNO in Hb), preserved tumor perfusion, and raised the blood pressure. In contrast, native Hb reduced both tumor perfusion and heart rate independently of the oxygen concentration of the inhaled gas, and did not elicit hypertensive effects. Window chamber (to image tumor arteriolar reactivity in vivo) and hemodynamic measurements indicated that the preservation of tissue perfusion by micromolar concentrations of SNO-Hb is a composite effect created by reduced peripheral vascular resistance and direct inhibition of the baroreceptor reflex, leading to increased blood pressure. Overall, these results indicate that the properties of SNO-Hb are attributable to allosteric control of NO release by oxygen in central as well as peripheral issues.
Authors:
Pierre Sonveaux; Andrew M Kaz; Stacey A Snyder; Rachel A Richardson; L Isabel Cárdenas-Navia; Rodney D Braun; John R Pawloski; Gillian M Tozer; Joseph Bonaventura; Timothy J McMahon; Jonathan S Stamler; Mark W Dewhirst
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2005-05-05
Journal Detail:
Title:  Circulation research     Volume:  96     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-27     Completed Date:  2005-10-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1119-26     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects*
Female
Heart Rate / drug effects
Hemoglobins / administration & dosage,  pharmacology*
Neoplasms, Experimental / blood supply*
Nitric Oxide / physiology*
Oxygen / metabolism,  pharmacology*
Oxyhemoglobins / pharmacology
Rats
Rats, Inbred F344
Regional Blood Flow / drug effects
Grant Support
ID/Acronym/Agency:
5P20RR016439/RR/NCRR NIH HHS; CA40355/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/Oxyhemoglobins; 0/S-nitrosohemoglobin; 10102-43-9/Nitric Oxide; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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