Role of kinins in the endothelial protective effect of ischaemic preconditioning

Abstract

1 The aim of this study was to assess whether the protective e ect 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-¯ow ischaemia (¯ow rate of 1 ml min 71 ) followed by 20-min reperfusion, after which coronaries were precontracted with 0.1 mM U-46619, and the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 mM), compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 mM). 3 In untreated hearts, ischaemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts. The vasodilatation to SNP was una ected after ischaemiareperfusion. Preconditioning (5 min of zero-¯ow 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 nM [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 e ect on the vasodilatation produced by either 5-HT or SNP in sham hearts. Pretreatment with Hoe 140 did not block the protective e ect of ischaemic preconditioning on the 5-HT vasodilatation. In contrast, LLDBK halved the protective e ect 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 a ords 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.

Regulation of the kinin receptors after induction of myocardial infarction: a mini-review

“…Expression of B1R by cardiomyocytes under ischemic conditions has been identified by using B1R agonists and antagonists in in vitro and ex vivo models. Thus, ischemia-induced cardiac B1R stimulation was only indirectly demonstrated by the capacity to modulate positively or negatively noradrenaline release (12), by reduction of reperfusion arrhythmia (13) or by preservation of endothelium-dependent vasodilation (14). However, B1R induced by post-surgery stress could not be excluded in these studies.…”

Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart

“…In the past, we have used the present experimental model extensively to study the mechanisms involved in the endothelial protective effect of preconditioning [8][9][10]27]. The coronary flow rate and duration of ischemia were selected in the beginning to inflict a selective endothelial dysfunction, which was confirmed by the blunted coronary vasodilatation to the endothelium-dependent dilator, 5-HT [28], contrasting with the full response to the endothelium-independent vasodilator SNP.…”

“…The beneficial effect of preconditioning is not limited to cardiomyocytes, since it has been shown to protect the endothelium as well [4,5], in various experimental models including dog resistance coronary arteries in vivo [6], and rat conduit coronary arteries in vitro [7]. The mechanisms involved in the endothelial protective effect of preconditioning share several similarities with those involved in the cardioprotective effect: adenosine [8], des-Arg 9 -bradykinin [9], prostaglandin E 2 [10], and reactive oxygen species [11] have all been proposed as triggers of preconditioning, with ATPsensitive potassium channels [8] and ICAM-1 [12] as end-effectors, activation of protein kinase C (PKC) being an obligatory intermediate [10,12].…”

Novel Mode of Action of Angiotensin I Converting Enzyme Inhibitors

“…The induction and activation of the B 1 receptor could prove advantageous under various stressful conditions, ranging from infection to cardiovascular disorders (15). The B 1 receptor may protect the heart in ischemic preconditioning (40). Activation of B 1 receptors in an ischemic heart inhibited norepinephrine outflow and prevented potentially lethal ventricular fibrillation (41).…”