*4.2.1 Hypothalamic-pituitary-adrenal (HPA) axis*

When people cope with mental stress, the paraventricular nucleus of the hypothalamus will secrete corticotropin-releasing hormone, which will cause the anterior pituitary to secrete corticotropin, which will stimulate the adrenal cortex to produce cortisol. Decreased baroreceptor reflex sensitivity can lead to myocardial ischemia and even severe arrhythmia and sudden death. Broadley et al. [64] found that the application of metyrapone, a drug that blocks cortisol release, prevented mental stress-related endothelial dysfunction and reduced baroreflex sensitivity. In addition, Seldenrijk et al. [65] showed that, in healthy elderly populations, an enhanced cortisol response to stressful stress was associated with an increased risk of coronary artery calcification.

#### *4.2.2 Sympathetic nervous system*

During mental stress, the excitability of the cardiac sympathetic nervous system increases, and the activated sympathetic nervous system promotes the release of catecholamines (including epinephrine, norepinephrine, and dopamine), resulting in increased blood pressure, increased heart rate, increased myocardial contractility, and cardiac output (**Figure 1**) [63]. The study of Wittstein et al. [1] showed

#### *Stress-Induced Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.105584*

that under strong mental stress in patients with stress cardiomyopathy, the level of catecholamines increased rapidly, and the excitability of the sympathetic nervous system was significantly enhanced, which led to the disturbance of neurohumoral regulation, resulting in increased myocardial vitality, myocardial damage, myocardial reversibility and left ventricular dysfunction (**Figure 1**).

#### *4.2.3 Inflammatory factors*

Inflammation is closely related to mental stress and cardiovascular disease. When the body responds to mental stress, blood vessels constrict and blood flow increases, prompting white blood cells and platelets to release inflammatory mediators [56]. When the stress is weak, the body can play a defensive role through the inflammatory response. When the stress is strong, excessive inflammatory mediators lead to vascular endothelial damage, which further promotes inflammatory response and inflammatory mediators, as well as promotes inflammatory cells to infiltrate myocardial tissue, leading to myocardial ischemia necrosis and cardiovascular disease [56]. Hammadah et al. [56] showed that the levels of inflammatory factors such as interleukin-6, monocyte chemoattractant protein-1, and matrix metalloproteinase-9, increased in patients with heart disease after mental stress. The level of matrix metalloproteinase-9 was negatively correlated with cortisol after stress. In conclusion, the relationship between inflammation-related factors and MSIC remains to be further explored (**Figure 1**).

### *4.2.4 Gene polymorphisms*

Genetic factors are one of the important reasons for the onset of cardiovascular diseases. Mental and psychological diseases are also closely related to an individual's response to stressful stimuli. For example, the serotonin transporter gene (SLC6A4) polymorphism is associated with emotion regulation in humans, and S allele carriers cause more severe fear and anxiety under mental stress [50]. Studies on the Val66Met single nucleotide polymorphism of brain-derived neurotrophic factor (BDNF) have shown that BDNFMet/Val carriers have a higher incidence of cognitive and mental disorders and coronary heart disease [51, 66].
