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Current Topics in Pharmacology   Volumes    Volume 14 
The potential clinical application of protein kinase C beta II peptide inhibitor or Gö 6983 in vascular endothelial dysfunction
Qian Chen, Brian Rueter, Samuel Krass, Christopher Zambrano, Shawn Thomas, Catherine Prince, Brandon Bell, Vincent Chai, Jeffery Emrich, Lindon Young
Pages: 11 - 24
Number of pages: 14
Current Topics in Pharmacology
Volume 14 

Copyright © 2010 Research Trends. All rights reserved

Vascular endothelial dysfunction which is associated with increased oxidative stress and decreased endothelial-derived nitric oxide has been considered as a major initial event in various diseases, such as atherosclerosis, diabetes and ischemia/reperfusion (I/R) injury.  Previously we found that a broad-spectrum protein kinase C (PKC) inhibitor (i.e., Gö 6983) and a specific PKC beta II peptide inhibitor (PKC βII-) were cardioprotective in myocardial I/R injury.  However, the direct effects of Gö 6983 or PKC βII- on vascular endothelial dysfunction and the related leukocyte-endothelial interactions are still unclear.  The leukocyte rolling, adherence and transmigration were estimated by using intravital microscopy in rat mesenteric postcapillary venules.  We found that superfusion of NG -nitro-L-arginine-methyl-ester (L-NAME, 50 µM) induced endothelial dysfunction and significantly increased leukocyte-endothelial interactions within a 2 hour period compared to Krebs’ buffer control group (P<0.05).  By contrast, Gö 6983 (25 nM-200 nM) or PKC βII- (0.1 µM-10 µM) dose-dependently attenuated these interactions induced by L-NAME (P<0.05).  Moreover, histological evaluation of Gö 6983 (200 nM) or PKC βII- (10 µM) superfused mesenteric tissue exhibited significantly less leukocyte adherence and tissue transmigration, as well as significantly less intercellular adhesion molecule-1 expression compared to L-NAME group.  Finally, in a rat extracorporeal shock wave lithotripsy model, we demonstrated that PKC βII- (0.055-0.55 mg/kg) significantly decreased oxidative stress when hydrogen peroxide was measured directly from rat renal veins (P<0.05).  In summary, Gö 6983 or PKC βII- can decrease the proinflammatory responses in vascular endothelium and may provide a potential clinical treatment to prevent vascular endothelial dysfunction.
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