HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 106/4/1132    most recent 90542.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, F. Articles by Finkel, M. S. Search for Related Content PubMed PubMed Citation Articles by Chen, F. Articles by Finkel, M. S.

p38 MAP kinase inhibitor reverses stress-induced myocardial dysfunction in vivo

Departments of ¹Medicine, ²Physiology and Pharmacology, ³Psychiatry, and ⁴Statistics, West Virginia University, Morgantown; and ⁵Louis A. Johnson Department of Veterans Affairs Medical Center, Clarksburg, West Virginia

Submitted 18 April 2008 ; accepted in final form 9 February 2009

Recent clinical reports strongly support the intriguing possibility that emotional stress alone is sufficient to cause reversible myocardial dysfunction in patients. We previously reported that a combination of prenatal stress followed by restraint stress (PS+R) results in echocardiographic evidence of myocardial dysfunction in anesthetized rats compared with control rats subjected to the same restraint stress (Control+R). We now report results of our catheter-based hemodynamic studies in both anesthetized and freely ambulatory awake rats, comparing PS+R vs. Control+R. Systolic function [positive rate of change in left ventricular pressure over time (+dP/dt)] was significantly depressed (P < 0.01) in PS+R vs. Control+R both under anesthesia (6,287 ± 252 vs. 7,837 ± 453 mmHg/s) and awake (10,438 ± 741 vs. 12,111 ± 652 mmHg/s). Diastolic function (–dP/dt) was also significantly depressed (P < 0.05) in PS+R vs. Control+R both under anesthesia (–5,686 ± 340 vs. –7,058 ± 458 mmHg/s) and awake (–8,287 ± 444 vs. 10,440 ± 364 mmHg/s). PS+R also demonstrated a significantly attenuated (P < 0.05) hemodynamic response to increasing doses of the β-adrenergic agonist isoproterenol. Intraperitoneal injection of the p38 MAP kinase inhibitor SB-203580 reversed the baseline reduction in +dP/dt and –dP/dt as well as the blunted isoproterenol response. Intraperitoneal injection of SB-203580 also reversed p38 MAP kinase and troponin I phosphorylation in cardiac myocytes isolated from PS+R. Thus the combination of prenatal stress followed by restraint stress results in reversible depression in both systolic and diastolic function as well as defective β-adrenergic receptor signaling. Future studies in this animal model may provide insights into the basic mechanisms contributing to reversible myocardial dysfunction in patients with ischemic and nonischemic cardiomyopathies.

heart failure; emotional stress; hemodynamics