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Role of kinins in the endothelial protective effect of ischaemic preconditioning
Author(s) -
Bouchard JeanFrançois,
Chouinard Jérôme,
Lamontagne Daniel
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701619
Subject(s) - bradykinin , vasodilation , sodium nitroprusside , medicine , ischemia , endothelium , perfusion , ischemic preconditioning , anesthesia , nitric oxide , cardiology , receptor
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. Isolated hearts of the rat were exposed to a 30‐min low‐flow ischaemia (flow rate of 1 ml min −1 ) followed by 20‐min reperfusion, after which coronaries were precontracted with 0.1 μ M U‐46619, and the response to the endothelium‐dependent vasodilator, 5‐hydroxytryptamine (5‐HT, 10 μ M ), compared to that of the endothelium‐independent vasodilator, sodium nitroprusside (SNP, 3 μ M ). 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. Blockade of B 1 and B 2 receptors with either 3 n M [Lys 0 , Leu 8 , des‐Arg 9 ]‐bradykinin (LLDBK) or 10 n M 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. Perfusion with either bradykinin or des‐Arg 9 ‐bradykinin (1 n M ) 30 min before and lasting throughout the ischaemia protected the endothelium. 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.British Journal of Pharmacology (1998) 123 , 413–420; doi: 10.1038/sj.bjp.0701619