Levels of Anti-Stress Reactions
Protective mechanisms operate comprehensively and are implemented at two main levels: central and peripheral. These levels function synchronously: while the brain attempts to reduce overall neuroendocrine hyperactivation, local tissue factors rescue cells from apoptosis and necrosis.
- Central regulatory mechanisms. Executed in the brain. Their main goal is to inhibit excessive excitation. The following neurotransmitter systems participate:
- GABAergic;
- Dopaminergic;
- Opioid-ergic;
- Serotonergic.
- Peripheral mechanisms. Act directly in target organs and tissues. These include prostaglandins, adenosine, acetylcholine, and antioxidant defense factors.
How Peripheral Stress-Limiting Factors Work
The overall effect of all peripheral factors is tissue protection. They prevent stress-induced ischemia, gastrointestinal ulceration, dystrophic changes, and block the release of destructive lysosomal hydrolases.
Prostaglandins (Pg) Act as the primary modulators of catecholamines. Their main effects include:
- Inhibition of norepinephrine release from nerve terminals (via a Ca2+-dependent mechanism).
- Reduction of intracellular cAMP levels (inhibiting its synthesis and accelerating its degradation by activating phosphodiesterases).
- Direct vasodilation and a hypotensive effect.
- Natriuretic and antithrombotic actions.
Adenosine and Myocardial Protection Adenosine is a critical regulator of cellular energy supply. Myocardial protection is a classic example of its function. During stress, the sympathoadrenal system (SAS) releases excess catecholamines. This triggers coronary vasospasm and cardiomyocyte Ca2+ overload, leading to cardiotoxicity.
In response to hypoxia and increased cardiac workload, 5'-AMP accumulates in the heart. 5'-nucleotidase converts it into adenosine. Adenosine inhibits Ca2+ influx into cells, dilates coronary arteries (coronary vasodilation), and limits catecholamine toxicity.
Acetylcholine Its synthesis and release are also activated during stress. Functionally, acetylcholine exerts effects similar to adenosine, protecting organs from SAS hyperactivation.
Antioxidant Defense Factors
Any stress response is inevitably accompanied by the generation of reactive oxygen species (ROS) and the intensification of lipid peroxidation (LPO). To prevent free radicals from destroying cell membranes, the antioxidant defense system (AOS) is engaged as a key cellular defense link.
Antioxidant factors are divided into two groups:
- Enzymatic: superoxide dismutase (SOD), catalase, glutathione peroxidase.
- Non-enzymatic: tocopherols (vitamin E) and glutathione-containing compounds.
Principles of Stress Therapy
Medical management of severe stress-induced injury is based on two principles: optimizing central regulation and providing peripheral tissue protection.
Optimization of stress-initiating systems aims to correct the function of the sympathoadrenal system (SAS) and the hypothalamic-pituitary-adrenal (HPA) axis. Dysfunction may manifest as either hyperreactivity or an insufficient response. The severity of the reaction largely depends on the baseline functional state of the body and the emotional perception of the situation.
Pharmacological correction utilizes tranquilizers and beta-blockers. Their goal is to prevent maladaptive reactions, alleviate fear, tension, irritability, and psychasthenia. The primary objective of therapy is not the complete suppression of stress, but rather bringing SAS and HPA axis activity to a level strictly proportional to the magnitude of the stressor.