Adenosine kinase inhibitor GP515 attenuates hepatic leukocyte adhesion after hemorrhagic hypotension

The American Journal of Physiology
C BauerW A Buurman

Abstract

Adhesion of leukocytes to the vascular endothelium hallmarks a key event in neutrophil-mediated organ injury after ischemia-reperfusion. The autacoid adenosine has been shown to inhibit activated neutrophil function and to interfere with leukocyte-endothelial adherence. Its therapeutic use in ischemia-reperfusion, however, has been limited by severe cardiovascular side effects. We therefore investigated the effects of the adenosine kinase inhibitor GP515 in vivo on hepatic leukocyte-endothelial interactions in a rat model of hemorrhagic hypotension and resuscitation, using intravital microscopy. Rats were pretreated with either GP515 (0.25 mg/kg) or saline in a randomized and blinded manner and subjected to pressure-controlled hemorrhagic hypotension at a mean arterial pressure of 40 mmHg for 60 min followed by 5 h of resuscitation. Five hours after resuscitation in saline-treated animals, firm leukocyte-sinusoidal adhesion was strongly enhanced in the periportal and midzonal sublobular regions, and sinusoidal diameters were also markedly reduced. Compared with saline treatment, GP515 significantly attenuated shock and resuscitation-induced leukocyte adhesion in both sublobular regions. Moreover, although GP515 did not signific...Continue Reading

References

Aug 1, 1992·Naunyn-Schmiedeberg's Archives of Pharmacology·D NolteK Messmer
Jun 1, 1991·The British Journal of Surgery·C R WelbournH B Hechtman
Feb 9, 1989·The New England Journal of Medicine·S J Weiss
Jul 1, 1989·Progress in Cardiovascular Diseases·L BelardinelliR M Berne
Feb 1, 1986·Clinical Physiology·B B Fredholm, A Sollevi
Sep 1, 1986·The Journal of Clinical Investigation·B N CronsteinR Hirschhorn
Oct 1, 1985·Archives of Surgery·R J GorisJ S Gimbrère
Aug 1, 1995·Arthritis and Rheumatism·B N CronsteinG Firestein
Aug 1, 1993·American Journal of Respiratory Cell and Molecular Biology·A WollnerJ B Smith
Jan 1, 1993·Cardiovascular Research·M B FormanE K Jackson

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Citations

Jul 21, 2020·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Anoek L I van LeeuwenCharissa E van den Brom

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