The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes.

AMP kinase (AMPK) plays an important role in the regulation of energy metabolism in cardiac cells. Furthermore, activation of AMPK protects the heart from myocardial infarction and heart failure. The present study examines whether or not AMPK affects the peroxisome proliferator-activated receptor-α (PPARα)/mitochondria pathway in response to acute oxidative stress in cultured cardiomyocytes. Cultured H9c2 rat embryonic cardioblasts were exposed to H2O2-induced acute oxidative stress in the presence or absence of metformin, compound C (AMPK inhibitor), GW6471 (PPARα inhibitor), or A-769662 (AMPK activator). Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death. In addition, metformin attenuated reactive oxygen species generation and depolarization of the inner mitochondrial membrane. The antioxidative effects of metformin were associated with the prevention of mitochondrial DNA damage in cardiomyocytes. Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARα and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation. The beneficial effects of metformin were not due to acetylation or phosphorylation of PPARα in response to oxidative stress. In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARα-CypD interactions, independent of phosphorylation and acetylation of PPARα and CypD.

Psychophysiological correlates of individual differences in patterns of hemodynamic reactivity.

The present study delineates a method for the quantification of six hemodynamic reactivity patterns, in response to a laboratory stressor, and examines the psychophysiological correlates of individual differences in these patterns. One hundred and ninety-four young adult men and women participated in rest periods and two laboratory stressors, mental arithmetic and an anger recall interview. Measures were taken of blood pressure, heart rate, and cardiac output, from which total peripheral resistance was derived, as well as state reports of feelings during the tasks. Six hemodynamic reactor patterns were identified: Non-reactors, Mild Myocardials, Mild Vasculars, Myocardials, Vasculars, and Dual Reactors, each associated with a unique profile of cardiac output and total peripheral resistance change. Myocardial reactors to the interview had the highest resting levels of blood pressure and total peripheral resistance. Dual reactors had the largest increases in diastolic reactivity; Dual and Myocardial reactors had the largest increases in systolic reactivity. The extreme reactor groups (Dual, Myocardial, Vascular) all reported greater task invigoration than the Non-reactors, who reported greater efforts to relax. Reactor groups were similar on anger-related trait affect. Based on both resting blood pressure and magnitude of task-induced reactivity, Myocardial and Dual reactors may be at the greatest risk for subsequent hypertension.

Family history of hypertension: a psychophysiological analysis.

Family history of hypertension (positive and negative) and gender groups were compared on cardiovascular responses at rest, during stressors and during recovery. Two tasks were employed, mental arithmetic and an anger recall interview. Both levels and reactivity measures of blood pressure, heart rate, cardiac output and total peripheral resistance were included. In addition, participants filled out several questionnaires measuring state feelings during the task and recovery periods, trait anger/hostility and emotions. Both men and women with a positive family history of hypertension exhibited higher tonic levels of blood pressure and heart rate at rest, recovery and during both tasks. They also exhibited greater heart rate reactivity during the mental arithmetic task and greater blood pressure reactivity to both tasks when post-math recovery, but not initial rest, was used as a covariate. Positive family history individuals reported less trust and gregariousness, more depression and aggression, less awareness of somatic responses to the tasks and less effort to relax during the post-task rest periods. Finally, significant correlations were found between low anger expression how anger experience and high anger control and task SBP levels in positive family history individuals.

Affect intensity and cardiac arousal.

Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990).