Mechanisms of protection afforded by preconditioning to endothelial
function against ischemic injury.
Bouchard, Jean-Fran[cedilla]cois, and Daniel Lamontagne.
Facult[acute]e de pharmacie, Universit[acute]e de Montr[acute]eal,
C.P. 6128, Succursal Centre-ville, Montr[acute]eal (Qu[acute]ebec),
Canada, H3C 3J7
APStracts 3:0175H, 1996.
The aim of this study was to assess whether the cardioprotective
effect of ischemic preconditioning (IPC) on endothelial function in
resistance coronary arteries of the rat involves adenosine and/or
activation of ATP-sensitive K+ channels (KATP channels). Isolated rat
hearts perfused under constant flow conditions were exposed to 30 min
of partial ischemia (flow rate 1 ml/min) followed by 20 min of
reperfusion. Preconditioning was performed with 5 min ischemia and 10
min reperfusion before the 30-min ischemia. After the 20-min
reperfusion period, coronaries were precontracted with U-46619
0.1[mu]M, and the coronary response to the endothelium-dependent
vasodilator, serotonin (5-HT, 10[mu]M), was compared to that of the
endothelium-independent vasodilator, sodium nitroprusside (SNP,
3[mu]M). KATP channels or adenosine receptors were blocked with
perfusion of either glibenclamide 0.3[mu]M or 8-phenyltheophylline
5[mu]M (8-PT) respectively, starting 15 min before IPC or a
corresponding sham period. In untreated hearts, ischemia diminished
selectively 5-HT-induced vasodilation, compared to sham hearts
(without ischemia). The vasodilation by SNP was unaffected after
ischemia and reperfusion. Preconditioning in untreated hearts
preserved the vasodilation produced by 5-HT. Treatment of hearts with
either glibenclamide or 8-PT halved the vasodilation produced by both
5-HT and SNP in sham hearts. Glibenclamide reduced by half, whereas
8-PT completely blocked the protective effect of IPC on endothelium
-dependent vasodilation. These results suggest that IPC affords
protection to endothelial function in resistance coronary arteries of
the rat partially by activation of KATP channels. Adenosine plays a
major role in that protection.
Received 13 November 1995; accepted in final form 15 April 1996.
APS Manuscript Number H1064-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96