| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Medical Pharmacology and Physiology, and the Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri
Submitted 11 July 2006 ; accepted in final form 24 August 2006
Preconditioning (PC) with nitric oxide (NO) donors or agents that increase endothelial NO synthase (eNOS) activity 24 h before ischemia-reperfusion (I/R) prevents postischemic leukocyte rolling (LR) and stationary leukocyte adhesion (LA). Since 5'-AMP-activated protein kinase (AMPK) phosphorylates eNOS at Ser1177, resulting in activation, we postulated that AMPK activation may trigger the development of a preconditioned anti-inflammatory phenotype similar to that induced by NO donors. Wild-type (WT) C57BL/6J and eNOS–/– mice were treated with the AMPK agonist 5-aminoimidazole-4-carboxamide 1-
-D-furanoside (AICAR) 30 min (early AICAR PC) or 24 h (late AICAR PC) before I/R; LR and LA were quantified in single postcapillary venules in the jejunum using intravital microscopy. I/R induced comparable marked increases in LR and LA in WT and eNOS–/– mice relative to sham-operated (no ischemia) animals. Late AICAR PC prevented postischemic LR and LA, whereas early AICAR PC prevented LA in WT mice. Late AICAR PC was ineffective in preventing I/R-induced LR but not LA in the eNOS–/– mice, and the same pattern was seen in WT animals treated with the NOS inhibitor N
-nitro-L-arginine. Early AICAR PC remained effective in preventing LA in eNOS–/– mice. Our results indicate that both early and late PC with an AMPK agonist produces an anti-inflammatory phenotype in postcapillary venules. Since the protection afforded by late AICAR PC on postischemic LR was prevented by NOS inhibition in WT mice and absent in eNOS-deficient mice, it appears that eNOS triggers this protective effect. In stark contrast, antecedent AMPK activation prevented I/R-induced LA by an eNOS-independent mechanism.
ischemia; reperfusion; leukocyte rolling and adhesion; endothelial nitric oxide synthase-deficient mice
This article has been cited by other articles:
|
|
 |
|
  M. Foller, M. Sopjani, S. Koka, S. Gu, H. Mahmud, K. Wang, E. Floride, E. Schleicher, E. Schulz, T. Munzel, et al. Regulation of erythrocyte survival by AMP-activated protein kinase FASEB J, April 1, 2009; 23(4): 1072 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yusof, K. Kamada, T. Kalogeris, F. S. Gaskin, and R. J. Korthuis Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H868 - H876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-A. Ewart, C. F. Kohlhaas, and I. P. Salt Inhibition of Tumor Necrosis Factor {alpha}-Stimulated Monocyte Adhesion to Human Aortic Endothelial Cells by AMP-Activated Protein Kinase Arterioscler. Thromb. Vasc. Biol., December 1, 2008; 28(12): 2255 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhao, J. W. Zmijewski, E. Lorne, G. Liu, Y.-J. Park, Y. Tsuruta, and E. Abraham Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L497 - L504. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
