L-NAME and L-arginine differentially ameliorate cigarette smoke-induced emphysema in mice.

Abstract

Nitric oxide (NO) represents one of the most important intra- and extracellular mediators and takes part in both biologic and pathologic processes. This study aimed to verify the treatment with an NO inhibitor and an NO substrate in pulmonary emphysema induced by cigarette smoke (CS) in a murine model. We compared N-acetylcysteine (NAC), a precursor of glutathione, to G-nitro-L-arginine-methyl ester or L-NAME (LN), which is an NO inhibitor, and to l-arginine (LA), which is a substrate for NO formation. Mice were divided into several groups: control, CS, CS + LN, CS + LA, and CS + NAC. Control and CS groups were treated daily with a vehicle, while CS + LN, CS + LA, and CS + NAC groups were treated daily with LN (60 mg/kg), LA (120 mg/kg) and NAC (200 mg/kg), respectively. The bronchoalveolar lavage was analyzed and the lungs were removed for histological and biochemical analysis. CS increases neutrophil number. Neutrophil number was lowest in CS + LN, followed by CS + LA. The lungs of CS + LN, CS + LA and CS + NAC mice were protected compared to the lungs of CS mice, but not equal to the quality of lungs in control mice. The CS group also exhibited increased oxidative stress, which was also present in the CS + LN group and to a lesser extent in the CS + LA group. Tissue inhibitor of metalloproteinase 1 and 2 increased in the CS + LN group and to a lesser extent in the CS + LA group relative to the control group. These results suggest that LN and LA treatment protected the mouse lung from CS. However, NAC treatment was more than LN and LA. We suggest that the protection conferred by LN treatment requires a balance between proteases and antiproteases, and that protection conferred by LA treatment involves the balance between oxidants and antioxidants.

• Authors: Samuel Santos Valença, Carlos Romualdo Rueff-Barroso, Wagner Alves Pimenta, Adriana Correa Melo, Renata Tiscoski Nesi, Marco Aurélio Santos Silva, Luís Cristóvão Porto
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 24 Issue 5 Pg. 587-94 (Oct 2011) ISSN: 1522-9629 [Electronic] England
• PMID: 21624489 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Enzyme Inhibitors
• Free Radical Scavengers
• Oxidants
• Smoke
• Nitric Oxide
• Arginine
• NG-Nitroarginine Methyl Ester
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Antioxidants (metabolism)
• Arginine (pharmacology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Free Radical Scavengers (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• NG-Nitroarginine Methyl Ester (pharmacology)
• Neutrophils (metabolism)
• Nitric Oxide (metabolism)
• Oxidants (metabolism)
• Oxidative Stress (drug effects)
• Pulmonary Emphysema (etiology, prevention & control)
• Smoke (adverse effects)
• Smoking (adverse effects)
• Tobacco