Heat stress-induced protection of endothelial function against ischaemic injury is abolished by ATP-sensitive potassium channel blockade in the isolated rat heart

1 The protection conferred by heat stress (HS) against myocardial ischaemia -reperfusion injury, in terms of mechanical function preservation and infar ct size reduction, is well documented and mechanisms underlying these effec ts have been extensively explored. However, the effect of HS on coronary ci rculation is less known. The aim of this study was thus to investigate the role of ATP-sensitive potassium (K-ATP) channels in the protection against ischaemic injury afforded by HS to the coronary endothelial function. 2 Twenty-four hours after whole body hyperthermia (42 degrees C for 15 min, H groups) or sham anaesthesia (Sham groups), isolated perfused rat hearts were subjected to a 15 min stabilization period followed by a 30 min infusi on of either 0.3 mu M glibenclamide (Gli, a K-ATP channel blocker) or its v ehicle (V). Hearts were then exposed to a low-flow ischaemia (30 min)-reper fusion (20 min) (I/R) or normally perfused (50 min), after which coronaries were precontracted with 0.1 mu M U-46619. Finally, the response to the end othelium-dependent vasodilator, 5-hydroxytryptamine (5-MT, 10 mu M) was com pared to that of the endothelium-independent vasodilator, sodium nitropruss ide (SNP, 3 mu M). 3 In hearts from Sham-V and Sham-Gli groups, I/R selectively diminished 5-H T-induced vasodilatation without affecting the vasodilatation to SNP. In V- treated groups, prior HS preserved the vasodilatation produced by 5-MT. Thi s MS-induced protection was abolished by Gli treatment. 4 In conclusion, these results suggest that K-ATP channel activation contri butes to the preservation of coronary endothelial function conferred by hea t stress against ischaemic insult.