Left ventricular stretch stimulates angiotensin II-mediated phosphatidylinositol hydrolysis and protein kinase C ε isoform translocation in adult guinea pig hearts

Karamchand Paul, Nancy A. Ball, Gerald W. Dorn, Richard A. Walsh

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Stretch of neonatal cardiomyocytes activates phospholipase C with production of inositol trisphosphate and diacylglycerol in part by formation of angiotensin II (Ang II). However, the response of this pathway to physical stimuli in the adult heart is poorly understood. Thus, in isovolumic perfused guinea pig hearts, we characterized stretch-mediated phosphatidylinositol (PI) hydrolysis and protein kinase C (PKC) isoform translocation using elevated diastolic pressure. Balloon dilatation (minimum diastolic pressure, 25 mm Hg) of the left ventricle (LV) stimulated PI hydrolysis. Pretreatment of stretched hearts with the specific angiotensin (AT1) receptor antagonist losartan abolished stretch-mediated accumulation of inositol phosphates. To examine PKC isoform expression and activation under these conditions, whole- heart extracts were examined by immunoblot analysis. Ang II translocated PKCε to the particulate fraction. 4β-Phorbol 12-myristate 13-acetate but not an inactive congener translocated PKCε to the particulate fraction and produced a decrease in myocardial contractile function. Mechanical stretch also translocated PKCε to the particulate fraction; however, this was attenuated but not abolished by losartan. We conclude that in the adult heart, LV dilatation produced stretch-mediated activation of phospholipase C, which resulted in PI hydrolysis and PKCε activation in part by stimulation of the local renin angiotensin system. In contrast to stretch-mediated inositol phosphate accumulation, PKCε translocation is not prevented by AT1 receptor blockade, indicating that this PKC isoform can be activated in response to mechanical deformation by an Ang II-independent mechanism in the adult myocardium.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalCirculation research
Volume81
Issue number5
DOIs
StatePublished - 1997

Keywords

  • Angiotensin II
  • Inositol phosphate
  • Protein kinase C
  • Signal transduction
  • Stretch

Fingerprint

Dive into the research topics of 'Left ventricular stretch stimulates angiotensin II-mediated phosphatidylinositol hydrolysis and protein kinase C ε isoform translocation in adult guinea pig hearts'. Together they form a unique fingerprint.

Cite this