Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation

Autor: Roland Prondzinsky, Bernd Niemann, Christian-Friedrich Vahl, Justin M. Carter, Karl Werdan, Axel Schlitt, Michael Buerke, Ute Buerke, Joachim Makowski, Susanne Rohrbach, Martin Russ, Manfred Dahm, Schulze C, Diethard Pruefer
Rok vydání: 2008
Předmět:
Zdroj: British Journal of Pharmacology. 153:1678-1685
ISSN: 0007-1188
DOI: 10.1038/sj.bjp.0707647
Popis: Background and purpose: The Na+/H+ exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca2+ overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. Experimental approach: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 μ ml−1) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min). Key results: Treatment with cariporide (10 mg kg−1 i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54±6.2 to 2.4±1.0 cells min−1, P
Databáze: OpenAIRE