Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

摘要: Aims This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection mice with targeted disruption sEH or Ephx2 gene (sEH null). Methods and results Isolated mouse hearts were perfused Langendorff mode subjected to global no-flow ischaemia followed by reperfusion. Hearts analysed for recovery left ventricular developed pressure (LVDP), mRNA levels, protein expression. Naive from null had similar expression preproBNP (Nppb) compared wild-type (WT) hearts. However, significant increases Nppb BNP occurred during post-ischaemic reperfusion correlated improved LVDP. Perfusion putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic prior reduced Inhibitor studies demonstrated that perfusion type-A (NPR-A) antagonist, A71915, limited recombinant full-length (rBNP)- 11,12-EET-perfused as well mice. Increased phosphorylated kinase C e Akt found WT either 11,12-EET rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower same samples. Furthermore, treatment phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished LVDP 11,12-EET-treated but not did inhibit rBNP-treated hearts. Conclusion Taken together, these data indicate EET-mediated involves PI3K signalling events.