Alterations of Load-Induced p38 MAP Kinase Activation in Failing Rat Hearts

Hemodynamic load-induced cardiac p38 mitogen-activated protein kinase (MAPK) activation was studied in normotensive control Dahl rats (n = 10) and hypertensive Dahl rats with heart failure (n = 16). The isolated heart from each animal was stretched on a Langendorff apparatus at an equivalent diastol...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-07, Vol.285 (2), p.503-507
Main Authors: Yasaka, Asuka, Hayashida, Wataru
Format: Article
Language:English
Subjects:
angiotensin II
Animals
Antihypertensive Agents - pharmacology
Body Weight
Diastole
Enzyme Activation
Heart - drug effects
Heart - physiology
Heart - physiopathology
heart failure
Heart Failure - enzymology
Heart Failure - physiopathology
Hemodynamics - physiology
hypertension
In Vitro Techniques
mitogen-activated protein kinase
Mitogen-Activated Protein Kinases - metabolism
Myocardial Contraction - drug effects
Myocardial Contraction - physiology
Myocardium - enzymology
Organ Size
p38 Mitogen-Activated Protein Kinases
Rats
Rats, Inbred Dahl
Reference Values
signal transduction
Systole
Tetrazoles - pharmacology
Valine - analogs & derivatives
Valine - pharmacology
Valsartan
Ventricular Function, Left
ventricular remodeling
Weight-Bearing
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Summary:Hemodynamic load-induced cardiac p38 mitogen-activated protein kinase (MAPK) activation was studied in normotensive control Dahl rats (n = 10) and hypertensive Dahl rats with heart failure (n = 16). The isolated heart from each animal was stretched on a Langendorff apparatus at an equivalent diastolic wall stress, and the p38-MAPK activity of the left ventricular (LV) myocardium was analyzed by immunoprecipitation-kinase assay. Compared to the control hearts, the stretch-induced p38-MAPK activities were significantly decreased, and inversely correlated with the LV diameter (r = −0.73, P < 0.01). Chronic treatment with an angiotensin II AT1-receptor antagonist, valsartan (10 mg/kg/day), ameliorated cardiac function and remodeling process in the failing hearts, which was associated with an improvement of the p38-MAPK activities. Thus, the mechano-signal transduction of p38-MAPK pathway is downregulated in the failing hearts, along with progressive ventricular remodeling. The data also suggest that the beneficial effects of the AT1-receptor antagonists are potentially mediated by the restoration of cardiac growth-related signal transduction.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5174