Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice
| Autor: | Rolf Bräuer, Laura Glück, Hans-Georg Schaible, Anne-Katja Imhof, Mieczyslaw Gajda, Stefan Schulz |
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| Jazyk: | angličtina |
| Předmět: |
medicine.hormone
Nociception musculoskeletal diseases Ambrisentan Endothelin A Receptor Antagonists Endothelin B Receptor Antagonists Immunology Anti-Inflammatory Agents Arthritis Administration Oral Pharmacology Endothelins Mice Rheumatology Ganglia Spinal Secondary Prevention Medicine Animals Edema Immunology and Allergy Sulfonamides Phenylpropionates business.industry Endothelin receptor antagonist Bosentan medicine.disease Arthralgia Arthritis Experimental Mice Inbred C57BL Pyridazines Disease Models Animal cardiovascular system Female business Endothelin receptor medicine.drug Research Article |
| Zdroj: | Arthritis Research & Therapy |
| ISSN: | 1478-6354 |
| DOI: | 10.1186/ar3372 |
| Popis: | Introduction Endothelins are involved in tissue inflammation, pain, edema and cell migration. Our genome-wide microarray analysis revealed that endothelin-1 (ET-1) and endothelin-2 (ET-2) showed a marked up-regulation in dorsal root ganglia during the acute phase of arthritis. We therefore examined the effects of endothelin receptor antagonists on the development of arthritis and inflammatory pain in monoarthritic mice. Methods Gene expression was examined in lumbar dorsal root ganglia two days after induction of antigen-induced arthritis (AIA) using mRNA microarray analysis. Effects of drug treatment were determined by repeated assessment of joint swelling, pain-related behavior, and histopathological manifestations during AIA. Results Daily oral administration of the mixed ETA and ETB endothelin receptor antagonist bosentan significantly attenuated knee joint swelling and inflammation to an extent that was comparable to dexamethasone. In addition, bosentan reduced inflammatory mechanical hyperalgesia. Chronic bosentan administration also inhibited joint swelling and protected against inflammation and joint destruction during AIA flare-up reactions. In contrast, the ETA-selective antagonist ambrisentan failed to promote any detectable antiinflammatory or antinociceptive activity. Conclusions Thus, the present study reveals a pivotal role for the endothelin system in the development of arthritis and arthritic pain. We show that endothelin receptor antagonists can effectively control inflammation, pain and joint destruction during the course of arthritis. Our findings suggest that the antiinflammatory and antinociceptive effects of bosentan are predominantly mediated via the ETB receptor. |
| Databáze: | OpenAIRE |
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