Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function
Open Access
- 28 April 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 83 (2), 362-370
- https://doi.org/10.1093/cvr/cvp134
Abstract
This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.Keywords
This publication has 43 references indexed in Scilit:
- Glycogen Synthase Kinase 3 Inhibition Slows Mitochondrial Adenine Nucleotide Transport and Regulates Voltage-Dependent Anion Channel PhosphorylationCirculation Research, 2008
- Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxiaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injuryProstaglandins & Other Lipid Mediators, 2007
- Diazoxide acts more as a PKC‐ɛ activator, and indirectly activates the mitochondrial KATP channel conferring cardioprotection against hypoxic injuryBritish Journal of Pharmacology, 2006
- Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanismsThe Journal of Physiology, 2006
- Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile FunctionCirculation Research, 2006
- Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vesselsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Autocrine and paracrine actions of natriuretic peptides in the heartPharmacology & Therapeutics, 2004
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Interleukin-1β Regulation of the Human Brain Natriuretic Peptide Promoter Involves Ras-, Rac-, and p38 Kinase–Dependent Pathways in Cardiac MyocytesHypertension, 1999