Document Detail


Rate of NO scavenging alters effects of recombinant hemoglobin solutions on pulmonary vasoreactivity.
MedLine Citation:
PMID:  12235032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many hemoglobin-based oxygen carriers (HBOCs) produce systemic and pulmonary hypertension and may increase microvascular permeability as a consequence of nitric oxide (NO) scavenging. In this study, we examined the effects of two recombinant human hemoglobin solutions, rHb1.1 and rHb2.0 for injection (rHb2.0), with different rates of NO scavenging on vasoconstrictor reactivity and vascular permeability in isolated, saline-perfused rat lungs. We hypothesized that rHb1.1, a first-generation HBOC with an NO scavenging rate similar to that of native human hemoglobin, would exacerbate pulmonary vasoconstriction and permeability and that rHb2.0, a second-generation HBOC with an NO scavenging rate approximately 20- to 30-fold lower than that of rHb1.1, would minimally influence these responses. Consistent with this hypothesis, rHb1.1 enhanced pulmonary vasoconstrictor reactivity to both hypoxia and thromboxane mimetic U-46619 in a dose-dependent fashion. In contrast, rHb2.0 produced little or no change in reactivity to these stimuli. Furthermore, whereas rHb1.1 abrogated pulmonary vasodilation to the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP), dose-dependent responses to SNAP were preserved, albeit attenuated, in lungs treated with rHb2.0. Finally, the capillary filtration coefficient was unaltered by either rHb1.1 or rHb2.0. We conclude that pulmonary hemodynamic responses to rHb2.0 are greatly reduced compared with those observed with rHb1.1, consistent with rHb2.0 having a diminished capacity to scavenge NO. In addition, neither hemoglobin solution measurably altered microvascular permeability in this preparation.
Authors:
Thomas C Resta; Benjimen R Walker; Mark R Eichinger; Michael P Doyle
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  93     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2003-02-21     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1327-36     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-5218, USA. tresta@salud.umn.edu
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MeSH Terms
Descriptor/Qualifier:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / administration & dosage,  pharmacology
Animals
Anoxia / physiopathology
Capillary Permeability / drug effects
Dose-Response Relationship, Drug
Free Radical Scavengers / metabolism*
Hemoglobins / pharmacology*
Lung / anatomy & histology
Male
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Organ Size
Pulmonary Circulation / drug effects*
Rats
Rats, Sprague-Dawley
Recombinant Proteins / pharmacology
S-Nitroso-N-Acetylpenicillamine / pharmacology
Solutions
Vascular Resistance / drug effects
Vasoconstriction / drug effects
Vasomotor System / drug effects*
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Hemoglobins; 0/Nitric Oxide Donors; 0/Recombinant Proteins; 0/Solutions; 10102-43-9/Nitric Oxide; 76898-47-0/15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; 79032-48-7/S-Nitroso-N-Acetylpenicillamine

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


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