Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) attenuates remobilization-induced joint inflammation.

Abstract

Shortly after joint remobilization, inflammation is induced in the joint and aggravates joint contracture via subsequent fibrosis. However, the mechanisms involved in remobilization-induced inflammation are not yet fully understood. We hypothesized that joint immobilization followed by remobilization induces hypoxia/reoxygenation, initiating inflammatory reactions through nitric oxide (NO) production via NO synthase 2 (NOS2). This study aimed to investigate whether: 1) administration of the NOS inhibitor L-NG-nitroarginine methyl ester (l-NAME) can attenuate remobilization-induced joint inflammation; and 2) hypoxia/reoxygenation is induced by joint immobilization and followed by remobilization. Unilateral knee joints of rats were immobilized using external fixators for three weeks. After removal of the fixation device, knees were allowed to move freely for one day (remobilization) with or without l-NAME administration. Without l-NAME administration, inflammatory reactions including joint swelling and inflammatory cell infiltration, edema, and upregulation of inflammatory mediator genes in the joint capsule were detected following upregulation of the NOS2 gene after remobilization. These remobilization-induced inflammatory reactions were partially attenuated by administration of l-NAME. Therefore, NOS2/NO elevation has potential as a novel treatment for remobilization-induced joint inflammation. Gene expression of the hypoxia marker hypoxia inducible factor-1α was upregulated after one day of remobilization, rather than after immobilization. These results suggest that upregulation of NOS2 by remobilization might be not due to hypoxia/reoxygenation.

• Authors: Akinori Kaneguchi, Junya Ozawa, Kengo Minamimoto, Kaoru Yamaoka
• Journal: Nitric oxide : biology and chemistry (Nitric Oxide) Vol. 96 Pg. 13-19 (03 01 2020) ISSN: 1089-8611 [Electronic] United States
• PMID: 31926320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Enzyme Inhibitors
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Cytokines (metabolism)
• Enzyme Inhibitors (therapeutic use)
• Inflammation (pathology, prevention & control)
• Joint Capsule (drug effects, pathology)
• Knee Joint (drug effects, pathology)
• Male
• NG-Nitroarginine Methyl Ester (therapeutic use)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, genetics)
• Rats, Wistar
• Up-Regulation (drug effects)