© 1997 American Heart Association, Inc.
Articles |
Left Ventricular Stretch Stimulates Angiotensin II– Mediated Phosphatidylinositol Hydrolysis and Protein Kinase C 
Isoform Translocation in Adult Guinea Pig Hearts
From the Division of Cardiology, Cardiovascular Center, University of Cincinnati (Ohio).
Correspondence to Richard A. Walsh, MD, Division of Cardiology, University of Cincinnati Medical Center, 231 Bethesda Ave, ML 542, Cincinnati, OH 45267. E-mail WALSHRA{at}UCBEH.SAN.UC.EDU
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 PKC to the particulate fraction. 4ß-Phorbol
12-myristate 13-acetate but not an inactive congener
translocated PKC to the particulate fraction and produced a decrease
in myocardial contractile function. Mechanical stretch also
translocated PKC 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 PKC activation
in part by stimulation of the local renin angiotensin
system. In contrast to stretch-mediated inositol phosphate
accumulation, PKC 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.
Key Words: signal transduction • stretch • inositol phosphate • protein kinase C • angiotensin II
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