Document Detail

Nitric oxide in the human respiratory cycle.
MedLine Citation:
PMID:  12042776     Owner:  NLM     Status:  MEDLINE    
Interactions of nitric oxide (NO) with hemoglobin (Hb) could regulate the uptake and delivery of oxygen (O(2)) by subserving the classical physiological responses of hypoxic vasodilation and hyperoxic vasconstriction in the human respiratory cycle. Here we show that in in vitro and ex vivo systems as well as healthy adults alternately exposed to hypoxia or hyperoxia (to dilate or constrict pulmonary and systemic arteries in vivo), binding of NO to hemes (FeNO) and thiols (SNO) of Hb varies as a function of HbO(2) saturation (FeO(2)). Moreover, we show that red blood cell (RBC)/SNO-mediated vasodilator activity is inversely proportional to FeO(2) over a wide range, whereas RBC-induced vasoconstriction correlates directly with FeO(2). Thus, native RBCs respond to changes in oxygen tension (pO2) with graded vasodilator and vasoconstrictor activity, which emulates the human physiological response subserving O(2) uptake and delivery. The ability to monitor and manipulate blood levels of NO, in conjunction with O(2) and carbon dioxide, may therefore prove useful in the diagnosis and treatment of many human conditions and in the development of new therapies. Our results also help elucidate the link between RBC dyscrasias and cardiovascular morbidity.
Timothy J McMahon; Richard E Moon; Ben P Luschinger; Martha S Carraway; Anne E Stone; Bryant W Stolp; Andrew J Gow; John R Pawloski; Paula Watke; David J Singel; Claude A Piantadosi; Jonathan S Stamler
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2002-06-03
Journal Detail:
Title:  Nature medicine     Volume:  8     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-01     Completed Date:  2002-08-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  711-7     Citation Subset:  IM    
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
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MeSH Terms
Anoxia / physiopathology
Erythrocytes / physiology
Hemodynamics / physiology*
Hemoglobins / metabolism*
Hyperoxia / physiopathology
Nitric Oxide / physiology*
Oxygen / blood
Respiratory Mechanics*
Respiratory System / blood supply*
Grant Support
Reg. No./Substance:
0/Hemoglobins; 10102-43-9/Nitric Oxide; 7782-44-7/Oxygen
Comment In:
Nat Med. 2003 May;9(5):481-2; author reply 482-3   [PMID:  12724738 ]
Nat Med. 2002 Jul;8(7):657-8   [PMID:  12091894 ]

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