Role of kinins in the endothelial protective effect of ischaemic preconditioning

1 The aim of this study was to assess whether the protective effect of ischaemic preconditioning on endothelial function in coronary arteries of the rat involves kinins. 2 Isolated hearts of the rat were exposed to a 30-min low-how ischaemia (flow rate of 1 ml min(-1)) followed by 20-min reperfusion, after which coronaries were precontracted with 0.1 mu M U-46619, and the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 mu M), compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 mu M). 3 In untreated hearts, ischaemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts. The vasodilatation to SNP was unaffected after ischaemia-reperfusion. Preconditioning (5 min of zero-flow ischaemia followed by 10 min reperfusion) in untreated hearts preserved the vasodilatation produced by 5-HT. 4 Blockade of B-1 and B-2 receptors with either 3 M [Lys(0), Leu(8), des-Arg(9)]-bradykinin (LLDBK) or 10 nM Hoe 140 (icatibant), respectively, (started 15 min before ischaemic preconditioning or a corresponding sham period and stopped just before the 20-min reperfusion period) had no effect on the vasodilatation produced by either 5-HT or SNP in sham hearts. Pretreatment with Hoe 140 did not block the protective effect of ischaemic preconditioning on the 5-HT vasodilatation. In contrast, LLDBK halved the protective effect of ischaemic preconditioning on endothelium-dependent vasodilatation. 5 Perfusion with either bradykinin or des-Arg(9)-bradykinin (1 nM) 30 min before and lasting throughout the ischaemia protected the endothelium. 6 In conclusion, ischaemic preconditioning affords protection to the endothelial function in coronary resistance arteries of the rat partly by activation of B-1 receptors. Although exogenous BK perfusion can protect the endothelium, B-2 receptors do not play an important role in this protection in the rat isolated heart.