Effects of Chronic Mild Stress on Cardiac Autonomic Activity, Cardiac Structure and Renin–Angiotensin–Aldosterone System in Male Rats

SIMPLE SUMMARY: Stress can cause heart disease by changing cardiac structure and/or function as assessed by heart rate variability; however, this may or may not happen when exposed to daily stress. Therefore, this study was conducted to investigate alterations in cardiac structure and cardiac control through autonomic activity, and in the renin–angiotensin–aldosterone system in male rats after exposure to 4-week chronic mild stress as an animal model for daily stress exposure in humans. The results showed that chronic mild stress increased both sympathetic and parasympathetic autonomic activities without affecting their balance. The renin–angiotensin–aldosterone system, which was partly responsible for changes in cardiac structure, was also affected. These data suggest that cardiac autonomic control and cardiac structure were affected by 4-week mild stress; however, this effect was probably in an adaptable period as the sympathetic and parasympathetic activities were in balance. ABSTRACT: Stress is associated with cardiovascular disease. One accepted mechanism is autonomic imbalance. In this study, we investigated the effects of chronic mild stress (CMS) on cardiac autonomic control, cardiac structure and renin–angiotensin–aldosterone system (RAAS) activity in adult male Sprague Dawley rats. The CMS model provides a more realistic simulation of daily stress. The animals were divided into control and CMS, and were exposed to 4-week mild stressors. The electrocardiogram recording, sucrose intake and parameters related to stress, cardiac alterations and RAAS were determined. The results showed that CMS had lower body weight and higher sucrose intake. The heart rate variability (HRV) revealed that CMS increased autonomic activity without affecting its balance. The increased RAAS activity with upregulated angiotensin type 1 receptor mRNA expression was shown in CMS. The increased sympathetic activity or RAAS was correlated with stress. Moreover, the altered cardiac structure (i.e., heart weight and cardiomyocyte cross-sectional area) were correlated with stress-, sympathetic- and RAAS-related parameters. These indicated that CMS-induced cardiac hypertrophy was the result of both sympathetic and RAAS activation. Therefore, it could be concluded that 4-week CMS in male rats induced negative emotion as shown by increased sucrose intake, and increased cardiac autonomic and RAAS activities, which may be responsible for mild cardiac hypertrophy. The cardiac hypertrophy herein was possibly in an adaptive, not pathological, stage, and the cardiac autonomic function was preserved as the autonomic activities were in balance.