Mechanisms of cardioprotection induced by preconditioning after activation of MITOK(ATP) channel / 中国应用生理学杂志

<p><b>AIM</b>To determine mechanisms of cardioprotection induced by combination angiotensin-converting enzyme inhibitors (ACEI) with subthreshold preconditioning after activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel.</p><p><b>METHODS</b>The Langendorff model of isolated rat heart was used. The time of the onset of uncoupling, the activities of sarcolemmal Na+/K+ -ATPase and Ca2+/Mg2+ -ATPase were measured.</p><p><b>RESULTS</b>The subthreshold preconditioning (2 min of ischemia and 10 min reperfusion) or captopril (an ACEI) alone did not protect hearts against injury of sustained ischemia. However combination captopril with subthreshold preconditioning increased LVDP. Pretreatment hearts with mitoK(ATP) channel inhibitor 5-HD abolished the protection effect. Combination captopril with subthreshold preconditioning delayed the onset of uncoupling, and enhanced the activities of sarcolemmal Na+/K+ ATPase and Ca2+/Mg2+ -ATPase in ischemia/reperfusion hearts. But 5-HD cancelled these cardioprotection effects.</p><p><b>CONCLUSION</b>Combination ACEI with subthreshold preconditioning delays the onset of cellular uncoupling induced by acute ischemia, and promotes the stability of sarcolemmal ion channels, in which activation of the mitoK(ATP) channels may be involved.</p>

Angiotensin-converting enzyme inhibitors potentiate subthreshold preconditioning through NO and mitoK(ATP) channel / 生理学报

The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) could contribute to the protective effects of preconditioning, and to explore its underlying mechanism. The Langendorff model of isolated rat heart was used. Cardiac contractility and lactate dehydrogenase (LDH) in the coronary effluent were measured, and infarct area of hearts after 30 min of ischemia followed by 120 min of reperfusion was analyzed. We found that: (1) The subthreshold preconditioning (2 min of ischemia and 10 min of reperfusion), captopril (an ACEI with sulfhydryl groups) or perindoprilate (an ACEI without sulfhydryl groups) alone did not protect the hearts from being injured by 30 min of ischemia and 120 min of reperfusion. (2) However, the combination of captopril or perindoprilate with subthreshold preconditioning could decrease left ventricular end-diastolic pressure (LVEDP), increase left ventricular developed pressure (LVDP) and coronary flow compared with the subthreshold preconditioned group. The combination treatments also inhibited the release of LDH from ischemia/reperfusion hearts, and reduced the infarct area in ischemic heart after 2 h of reperfusion (P<0.05). (3) By using NOS inhibitor L-NAME (100 mumol/L) before combined administration of ACEI with subthreshold preconditioning, the protection effect triggered by the combination treatment was significantly reduced. Pretreatment of the hearts with mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel inhibitor 5-HD (100 mumol/L) also abolished the protection effect (P<0.05). (4) Subthreshold preconditioning, captopril or perindoprilate alone could enhance the NO content in coronary effluent (P<0.05), but the combination of captopril or perindoprilate with subthreshold preconditioning could further augment the NO content compared with the subthreshold preconditioned group (P<0.05). The results indicate that ACEIs with or without sulfhydryl groups may potentiate the subthreshold preconditioning to trigger cardiac protection effect against the ischemia/reperfusion injury. This protection effect in the heart is possibly mediated by the generation of NO and the activation of mitoK(ATP) channel.