Document Detail


Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide.
MedLine Citation:
PMID:  21057038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erythrocyte free hemoglobin (Hb) induces vasoconstriction due to nitric oxide (NO) scavenging, limiting the NO available for vascular smooth muscle. The central objective of this study was to restore NO bioavailability using long-lived circulating NO-releasing nanoparticles (NO-np) to reverse the vasoconstriction and hypertension induced by polymerized bovine Hb (PBH) NO scavenging. PBH (13 g/dl) was infused in a volume equal to 10% of the animal blood volume. Intravascular NO supplementation was provided with an infusion of NO-np (10 and 20 mg/kg body wt). This study was performed using the hamster window chamber model to concurrently access systemic and microvascular hemodynamics. Infusion of PBH increased blood pressure and induced vasoconstriction. Treatment with 10 and 20 mg/kg NO-np reduced the blood pressure and vasoconstriction induced by PBH. Moreover, the higher dose of NO-np decreased blood pressure and induced vasodilation compared with baseline, respectively. Treatment with NO-np to decrease PBH-induced vasoconstriction increased methemoglobin levels and plasma nitrite and nitrate. In conclusion, NO-np counteracted both systemic hypertension and decreased the vasoconstrictor effects of PBH infusion, improving systemic and microvascular function. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent to replenish NO in situations where NO production is impaired, insufficient, or consumed, thereby preventing vascular complications.
Authors:
Pedro Cabrales; George Han; Parimala Nacharaju; Adam J Friedman; Joel M Friedman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-05
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  2014-06-02    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H49-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blood Pressure / drug effects
Cricetinae
Heart Rate / drug effects
Hemoglobins / administration & dosage*,  metabolism
Male
Mesocricetus
Microcirculation / drug effects
Nanoparticles
Nitric Oxide / administration & dosage*,  metabolism
Random Allocation
Vasoconstriction / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
P01-HL071064/HL/NHLBI NIH HHS; R01-HL062354/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobins; 31C4KY9ESH/Nitric Oxide
Comments/Corrections

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