0309 : Cardioprotective effect of a novel snake venom derived natriuretic peptide during myocardial ischemia reperfusion injury

Abstract

In this study, we aimed at testing the therapeutic potential of a novel Natriuretic Peptide (NPs), identified from Tunisian snake venom, when administered during reperfusion. Langendorff perfused male Wistar rat hearts were subjected to 30min regional coronary artery occlusion followed by 90min reperfusion. Hearts were treated either with brain natriuretic peptide BNP (10nM) or NPs (200nM). In another set of experiments, hearts were pretreated with either isatin (100μM), a natriuretic peptide receptors blocker or 5HD (10μM), a mitochondrial KATP channels blocker. Post ischemic cardiac haemodynamic parameters, using Labt Chart (ADInstruments) and infarct size (IS), using planimetry, were evaluated. Western blotting experiments for studying cGMP and Reperfusion Injury Salvage Kinases pathways were performed. Calcium Retention Capacity (CRC) to evaluate the mitochondrial function was also assessed by oxygraphy. BNP and NPs significantly decreased the IS by 60% and 62% respectively compared to control non treated hearts (p<0.001). Regarding hemodynamic parameters, both BNP and NPs improved the developed pressure (DP) by 135% and 152% respectively (p<0.05). These beneficial effects are abolished after pretreatment by isatin or 5HD. NPs significantly increased the expression of pAKT, pGSK3ß and PKCεwhen BNP increased pERK1/2 compared to control group. Both BNP and NPs increased the CRC by 124% and 86% respectively compared to control group. Our results demonstrate that NPs and BNP have cardioprotective effects during acute myocardial ischemia. These effects are mediated, for both drugs, by natriuretic receptors and by the activation of mitochondrial KATP channels. The cardioprotection involves the two PI3K/Akt/ERK and cGMP-PKC signaling pathways which converge to the mitochondria. Administration of NPs may provide a novel therapeutic strategy in acute myocardial isch