Recent clinical reports strongly support the intriguing possibility that emotional stress alone is sufficient to cause reversible myocardial dysfunction in patients. We have previously reported that a combination of pre-natal 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 (+dp/dt) was significantly depressed (p<0.01) in PS+R vs Control + R both under anesthesia (6,287 ± vs. 7837 ± 453) and awake (10,438 ± 741 vs 12,111 ± 652). 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) and awake (-8,287 ± 444 vs 10,440 ± 364). PS+R also demonstrated a significantly attenuated (p<0.05) hemodynamic response to increasing doses of the beta adrenergic agonist, isoproterenol. Intraperitoneal injection of the p38 MAP kinase inhibitor, SB203580, 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 phosphorylaton in cardiac myocytes isolated from PS+R. Thus, the combination of pre-natal stress followed by restraint stress results in reversible depression in both systolic and diastolic function, as well as, defective beta 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 non-ischemic cardiomyopathies.