Atp-sensitive k+ channels are not involved in ischemia/reperfusion
lung endothelial injury .
Khimenko, Pavel L., Timothy M. Moore, and Aubrey E. Taylor.
Department of Physiology, College of Medicine, University of South
Alabama, Mobile, Alabama 36688
APStracts 2:0151A, 1995.
The role of ATP-sensitive K+ channels (KATP) in ischemia and
reperfusion (I/R) was studied in isolated rat lungs. I/R produced a
six-fold increase in endothelial permeability as measured by the
capillary filtration coefficient (Kfc). Cromakalim (10 [mu]M), given
at 46 minutes after reperfusion reversed the Kfc increase. This
effect was not blocked by either a protein kinase A inhibitor (Rp
-cAMPS, 100 [mu]M) or an adenosine antagonist (SPT, 20 [mu]M).
Cromakalim, given before ischemia or at the beginning of reperfusion
protected the endothelial barrier from injury. Glibenclamide (500
[mu]M), given before the ischemic period, at the beginning of
reperfusion, or 46 minutes 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 [mu]M) 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-PKA system and
adenosine.
Received 20 January 1995; accepted in final form 29 March 1995.
APS Manuscript Number A75-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.