Journal of Applied Physiology, Vol 79, Issue 2 554-559, Copyright © 1995 by American Physiological Society

ARTICLES

ATP-sensitive K+ channels are not involved in ischemia-reperfusion lung endothelial injury

P. L. Khimenko, T. M. Moore and A. E. Taylor
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688, USA.

The role of ATP-sensitive K+ channels (KATP) in ischemia and reperfusion (I/R) was studied in isolated rat lungs. I/R produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Cromakalim (10 microM) given at 46 min after reperfusion reversed the filtration coefficient increase. This effect was not blocked by either a protein kinase A inhibitor (adenosine-3',5'-cyclic monophosphothioate; 100 microM) or an adenosine antagonist [8-(p-sulfophenyl)-theophylline; 20 microM]. Cromakalim given before ischemia or at the beginning of reperfusion protected the endothelial barrier from injury. Glibenclamide (500 microM) given before the ischemic period, at the beginning of reperfusion, or 46 min after reperfusion did not alter the changes in microvascular permeability produced by I/R. Glibenclamide blocked the ability of cromakalim to reverse endothelial damage but not the ability of either isoproterenol (10 microM) or an adenosine A2-receptor agonist, CGS-21680 (300 nM). We conclude that opening of KATP channels does not produce endothelial injury in I/R. The activation of KATP channels can both protect against and reverse the endothelial damage associated with I/R. This novel mechanism(s) is independent from known pathways that employ cAMP-protein kinase system and adenosine.

This article has been cited by other articles:

				C. Leroy, A. Dagenais, Y. Berthiaume, and E. Brochiero Molecular identity and function in transepithelial transport of KATP channels in alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L1027 - L1037. [Abstract] [Full Text] [PDF]

				T. Fukuse, T. Hirata, M. Omasa, and H. Wada Effect of Adenosine Triphosphate-Sensitive Potassium Channel Openers on Lung Preservation Am. J. Respir. Crit. Care Med., June 1, 2002; 165(11): 1511 - 1515. [Abstract] [Full Text] [PDF]

				P. Bentzer, L. Kongstad, and P.-O. Grande Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2697 - H2706. [Abstract] [Full Text] [PDF]

				J. M. Dodd-O and D. B. Pearse Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H303 - H312. [Abstract] [Full Text] [PDF]

				R. Liu, Y. Ishibe, M. Ueda, and Y. Hang Isoflurane Administration Before Ischemia and During Reperfusion Attenuates Ischemia/Reperfusion-Induced Injury of Isolated Rabbit Lungs Anesth. Analg., September 1, 1999; 89(3): 561 - 561. [Abstract] [Full Text] [PDF]

				L. F. Richard, T. E. Dahms, and R. O. Webster Adenosine prevents permeability increase in oxidant-injured endothelial monolayers Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H35 - H42. [Abstract] [Full Text] [PDF]

				M. Yamashita, R. A. Schmid, S. Fujino, J. D. Cooper, and G. A. Patterson NICORANDIL, A POTENT ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM-CHANNEL OPENER, AMELIORATES LUNG ALLOGRAFT REPERFUSION INJURY J. Thorac. Cardiovasc. Surg., November 1, 1996; 112(5): 1307 - 1314. [Abstract] [Full Text]