Document Detail

Intravascular infusion of acid promotes intrapulmonary inducible nitric oxide synthase activity and impairs blood oxygenation in rats.
MedLine Citation:
PMID:  12771618     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To test the hypothesis that intravascular acid infusion promotes intrapulmonary nitric oxide formation by promoting inducible nitric oxide synthase (iNOS) and inhibiting endothelial nitric oxide synthase (eNOS) expression in rats. DESIGN: Prospective, placebo controlled, randomized laboratory study. SETTING: University laboratory. SUBJECTS: Twelve male Sprague-Dawley rats weighing 317 +/- 30 g served as study subjects. All animals were anesthetized, paralyzed, and mechanically ventilated throughout the experiment. INTERVENTIONS: The animals were randomized to receive either 0.1 N hydrochloric acid or 0.9% saline intravenously. The infusions were initially given at a rate of 11 mL/kg/hr for 15 mins and then at a rate of 0.95 mL/kg/hr for the remainder of the experiment. Exhaled nitric oxide concentrations and hemodynamic measurements were monitored throughout the experiment. Lung tissues were harvested for Western blot analysis and immunostaining 4 hrs after starting the intravascular infusion. MEASUREMENT AND MAIN RESULTS: At the end of the experiment, we found more than a four-fold higher concentration of exhaled nitric oxide in the acid-treated animals than in the saline-treated animals (p <.001). Western blot analysis revealed that the acid infusion increased intrapulmonary iNOS concentrations (p <.001), yet it decreased intrapulmonary eNOS concentrations (p =.009). Acid-related lung injury manifested as a decrease in blood oxygen tensions (p =.045) and as an increase in lung homogenate interleukin-6 concentrations (p =.003). CONCLUSIONS: Our results reveal that hydrochloric acid infusion stimulates intrapulmonary nitric oxide formation at least in part by promoting the expression of iNOS. Our findings suggest that correcting acidosis should attenuate iNOS formation. Our data also support the idea that metabolic acidosis itself can lead to impaired intrapulmonary gas exchange and increased expression of pro-inflammatory cytokines such as interleukin-6. Whether the induction of intrapulmonary nitric oxide formation mediates or simply indicates lung injury warrants further investigation.
Ikram U Haque; Chun-Jen Huang; Philip O Scumpia; Omer Nasiroglu; Jeffrey W Skimming
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Critical care medicine     Volume:  31     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-28     Completed Date:  2003-06-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1454-60     Citation Subset:  AIM; IM    
Department of Pediatrics, University of Florida, Gainesville, USA.
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MeSH Terms
Acidosis / chemically induced*,  enzymology*,  immunology,  pathology
Blotting, Western
Breath Tests
Disease Models, Animal*
Enzyme-Linked Immunosorbent Assay
Hydrochloric Acid / adverse effects*
Infusions, Intravenous
Interleukin-6 / analysis
Least-Squares Analysis
Lung / chemistry*,  pathology
Nitric Oxide / analysis*
Nitric Oxide Synthase / analysis*
Nitric Oxide Synthase Type II
Prospective Studies
Pulmonary Gas Exchange
Random Allocation
Rats, Sprague-Dawley
Respiratory Distress Syndrome, Adult / chemically induced*,  enzymology*,  immunology,  pathology
Grant Support
5M01RR000082-390655/RR/NCRR NIH HHS
Reg. No./Substance:
0/Interleukin-6; 10102-43-9/Nitric Oxide; 7647-01-0/Hydrochloric Acid; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, rat

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

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