Document Detail


Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.
MedLine Citation:
PMID:  22426035     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.
Authors:
Edward A Pankey; Adeleke M Badejo; David B Casey; George F Lasker; Russel A Riehl; Subramanyam N Murthy; Bobby D Nossaman; Philip J Kadowitz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-14
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  27     ISSN:  1089-8611     ISO Abbreviation:  Nitric Oxide     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-12-14     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Cardiac Output / drug effects
Dose-Response Relationship, Drug
Hemodynamics / drug effects
Hypertension, Pulmonary / chemically induced,  drug therapy*,  pathology
Hypertrophy, Right Ventricular / drug therapy
Lung / drug effects,  pathology
Monocrotaline
Morpholines
Nitric Oxide / metabolism
Nitroprusside
Pyrimidines
Rats
Rats, Sprague-Dawley
Sodium Nitrite / pharmacology*
Tunica Media / drug effects,  pathology
Grant Support
ID/Acronym/Agency:
HL 62000/HL/NHLBI NIH HHS; HL 77421/HL/NHLBI NIH HHS; R01 HL062000-04A1/HL/NHLBI NIH HHS; R01 HL077421-04S1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/BAY 41-8543; 0/Morpholines; 0/Pyrimidines; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 315-22-0/Monocrotaline; 7632-00-0/Sodium Nitrite
Comments/Corrections

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