Stress-limiting systems

Levels of implementation of antistress reactions

Protective mechanisms work in a complex manner and are implemented at two main levels: central and peripheral. These levels function synchronously: while the brain attempts to reduce the overall hyperactivation of neuroendocrine pathways, local tissue factors rescue cells from death.

1. Central regulatory mechanisms. Implemented in the brain. Their main task is to inhibit excessive excitation. The following neurotransmitter systems participate in this:
2. GABAergic;
3. Dopaminergic;
4. Opioidergic;
5. Serotonergic.

1. Peripheral mechanisms. Act directly in the "effector" organs and tissues. These include prostaglandins, adenosine, acetylcholine, and antioxidant defense factors.

How peripheral stress-limiting factors work

The net effect of all peripheral factors comes down to tissue protection. They prevent stress-dependent ischemia, gastrointestinal ulceration, dystrophic changes, and also block the release of destructive lysosomal hydrolases.

Prostaglandins (Pg) Act as the main modulators of catecholamines. Their main effects include:

• Inhibition of noradrenaline release from nerve endings (via a Ca2+-dependent mechanism).
• Reduction of intracellular cAMP levels (they suppress its formation and accelerate its degradation by activating phosphodiesterases).
• Direct vasodilation and hypotensive effect.
• Natriuretic and antithrombotic action.

Adenosine and heart protection Adenosine is a crucial regulator of cellular energy supply. Myocardial protection is a classic example of its function. During stress, the sympathoadrenal system (SAS) releases an excess of catecholamines. This causes coronary vessel spasm and calcium overload of cardiomyocytes (Ca2+), leading to a cardiotoxic effect.

In response to hypoxia and increased workload, 5'-AMP accumulates in the heart. Under the action of the enzyme 5'-nucleotidase, it forms adenosine. It inhibits Ca2+ transport into cells, dilates coronary arteries (coronary vasodilation), and limits catecholamine toxicity.

Acetylcholine Its synthesis and release are also activated during stress. In its ultimate outcomes, acetylcholine exerts an effect 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 system (AOS)—a key link in cell defense—is engaged.

Antioxidant factors are divided into two groups:

• Enzymatic: superoxide dismutase (SOD), catalase, glutathione peroxidase.
• Non-enzymatic: tocopherols (vitamin E) and glutathione-containing substances.

Principles of therapy in stress

Medical management of severe stress-induced injuries is based on two principles: optimization of central regulation and peripheral tissue protection.

Optimization of the functions of stress-initiating systems aims to correct the activity of the sympathoadrenal (SAS) and hypothalamic-pituitary-adrenal (HPA) axes. Disorders can manifest as either hyperreactivity or an insufficient response. The severity of the response largely depends on the initial functional state of the body and the emotional perception of the situation.

For pharmacological correction, tranquilizers and beta-blockers are used. Their goal is to prevent inadequate responses, eliminate fear, tension, irritability, and psychasthenia. The main task of therapy is not the complete suppression of stress, but bringing the state of the SAS and HPA axis to a level strictly adequate to the strength of the acting stimulus.

Class and exam questions

What else to study on this topic

• Mechanisms for reducing intracellular cAMP levels under the action of prostaglandins.
• Biochemical stages of the adenosine cycle in the myocardium.
• The role of lysosomal hydrolases in the pathogenesis of stress-induced tissue damage.
• Enzymatic and non-enzymatic factors of cellular antioxidant defense.
• The use of tranquilizers and beta-blockers for correcting hyperreactivity.

Other topics in "Chapter 19. The Adaptive Process. Stress"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.