potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice强大的抗炎和antinociceptive活动monoarthritic内皮素受体拮抗剂应用波生坦的老鼠.pdfVIP

potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice强大的抗炎和antinociceptive活动monoarthritic内皮素受体拮抗剂应用波生坦的老鼠.pdf

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potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice强大的抗炎和antinociceptive活动monoarthritic内皮素受体拮抗剂应用波生坦的老鼠

Imhof et al. Arthritis Research Therapy 2011, 13:R97 /content/13/3/R97 RESEARCH ARTICLE Open Access Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice 1 1 2 2 3 1* Anne-Katja Imhof , Laura Glück , Mieczyslaw Gajda , Rolf Bräuer , Hans-Georg Schaible and Stefan Schulz Abstract 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 p

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