Participation of prostaglandin E2 in the endothelial protective effect of ischaemic preconditioning in isolated rat heart

Objective: To assess whether the protective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries of the rat involves prostaglandins. Methods: Isolated rat hearts perfused under constant how conditions were exposed to 30 min of partial ischaemia (flow-rate 1 ml/min) followed by 20 min of reperfusion, after which coronaries were precontracted with U-46619 0.1 mu M, and the coronary response to the endothelium-dependent vasodilator, serotonin (5-MT, 10 mu M), was compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 mu M) Prostaglandin production was blocked with a perfusion of indomethacin 10 mu M started 15 min before IPC or a corresponding sham period and stopped just before the 20-min reperfusion period. Results: In untreated hearts, ischaemia diminished selectively 5-MT-induced vasodilatation, compared to sham hearts. The vasodilatation by SNP was unaffected after ischaemia and reperfusion. IPC (5 min of zero-flow ischaemia followed by 10 min reperfusion before the 30-min partial ischaemia) preserved the vasodilatation produced by 5-MT. Enzyme-immunoassays showed an increased production of PGE, in the IPC group. Treatment of hearts with indomethacin blocked the protective effect of IPC on the vasodilatation produced by 5-HT and decreased the production of PGE,. A 5-min perfusion with 3 nM PGE, started 15 min before the partial ischaemia, protected the endothelium. This was blocked by 1 mu M chelerythrine, but not by 0.3 mu M glibenclamide. Conclusions: These results suggest that IPC affords protection to endothelial function in coronary arteries of the rat partially via the release of PGE,. Under our experimental conditions, the protective effect of PGE(2) is mediated by PKC. (C) 2000 Elsevier Science B.V. All rights reserved.