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

Ketul R. Chaudhary, Sri Nagarjun Batchu, Dipankar Das, Mavanur R. Suresh, J R Falck, Joan P. Graves, Darryl C. Zeldin, John M. Seubert

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

AimsThis 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).Methods and resultsIsolated 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.ConclusionTaken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.

Original languageEnglish (US)
Pages (from-to)362-370
Number of pages9
JournalCardiovascular Research
Volume83
Issue number2
DOIs
StatePublished - Jul 2009

Fingerprint

Brain Natriuretic Peptide
Acids
Ventricular Pressure
Messenger RNA
1-Phosphatidylinositol 4-Kinase
A 71915
Reperfusion
Ischemia
Perfusion
Glycogen Synthase Kinase 3
Protein Kinase C
Proteins

Keywords

  • B-type natriuretic peptide
  • Epoxyeicosatrienoic acid
  • GSK-3β
  • Ischaemia-reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function. / Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Falck, J R; Graves, Joan P.; Zeldin, Darryl C.; Seubert, John M.

In: Cardiovascular Research, Vol. 83, No. 2, 07.2009, p. 362-370.

Research output: Contribution to journalArticle

Chaudhary, Ketul R. ; Batchu, Sri Nagarjun ; Das, Dipankar ; Suresh, Mavanur R. ; Falck, J R ; Graves, Joan P. ; Zeldin, Darryl C. ; Seubert, John M. / Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function. In: Cardiovascular Research. 2009 ; Vol. 83, No. 2. pp. 362-370.
@article{82b2d559898048eca08e343e93e04bc7,
title = "Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function",
abstract = "AimsThis 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).Methods and resultsIsolated 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. Na{\"i}ve 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.ConclusionTaken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.",
keywords = "B-type natriuretic peptide, Epoxyeicosatrienoic acid, GSK-3β, Ischaemia-reperfusion",
author = "Chaudhary, {Ketul R.} and Batchu, {Sri Nagarjun} and Dipankar Das and Suresh, {Mavanur R.} and Falck, {J R} and Graves, {Joan P.} and Zeldin, {Darryl C.} and Seubert, {John M.}",
year = "2009",
month = "7",
doi = "10.1093/cvr/cvp134",
language = "English (US)",
volume = "83",
pages = "362--370",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

AU - Chaudhary, Ketul R.

AU - Batchu, Sri Nagarjun

AU - Das, Dipankar

AU - Suresh, Mavanur R.

AU - Falck, J R

AU - Graves, Joan P.

AU - Zeldin, Darryl C.

AU - Seubert, John M.

PY - 2009/7

Y1 - 2009/7

N2 - AimsThis 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).Methods and resultsIsolated 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.ConclusionTaken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.

AB - AimsThis 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).Methods and resultsIsolated 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.ConclusionTaken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.

KW - B-type natriuretic peptide

KW - Epoxyeicosatrienoic acid

KW - GSK-3β

KW - Ischaemia-reperfusion

UR - http://www.scopus.com/inward/record.url?scp=67650221165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650221165&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvp134

DO - 10.1093/cvr/cvp134

M3 - Article

VL - 83

SP - 362

EP - 370

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 2

ER -