As it was found out in the recent past, in addition to the obvious functions, the heart also performs the role of an organ of internal secretion. This aroused interest not only among medical theorists, but also among practitioners. Natriuretic peptides (NUP) have been isolated not only in the myocardium, but also in a number of other internal organs that have not previously been discredited by their endocrine functions. A collective decision was made to use quantitative indicators of NLP in the blood to predict the development of cardiac pathologies, since this method was the least invasive and simple for the patient.
Discovery of the endocrine function of the heart
Natriuretic peptides were discovered back in the eighties of the last century, when scientists noticed a connection between the expansion of the heart chambers and the intensity of urine secretion. The authors of the discovery initially considered this phenomenon to be a reflex and did not attach any importance to it.
Later, when pathomorphologists and histologists took up the study of this issue, they found out that in the cells of the tissue that makes up the atrium, there are inclusions containing protein molecules. It has been experimentally proven that an extract from the atria of rats produces a powerfuldiuretic effect. Then we managed to isolate the peptide and establish the sequence of amino acid residues that make it up.
Some time later, biochemists identified three separate components in this protein (alpha, beta and gamma), different not only in chemical structure, but also in their effects: alpha was stronger than the other two. Currently distinguished:
- atrial NUP (type A);
- cerebral NUP (type B);- urodilatin (type C).
Biochemistry of natriuretic peptide
All natriuretic peptides are similar in structure and differ only in the terminal nitrogenous radicals or the arrangement of carbon atoms. To date, all the attention of chemists is focused on NUP type B, since it has a more stable form in blood plasma, and also allows you to get more informative results. Atrial NUP plays the role of one of the correctors of the body's water and electrolyte balance. It is produced in the myocardium both in normal conditions and against the background of chronic heart failure.
It has been proven that the precursor of brain NUP consists of 108 amino acid residues synthesized by the cells of the left ventricle. When the molecule is laced from the cytoplasm, it is affected by the enzyme furin, which converts this protein into an active form (a total of 32 amino acids out of 108). Brain NUP exists in the blood for only 40 minutes, after which it decomposes. An increase in the synthesis of this protein is associated with an increase in the stretching of the walls of the ventricles and cardiac ischemia.
Removal of NUPs from plasmacarried out in two main ways:
- cleavage by lysosomal enzymes;- proteolysis.
The leading role is assigned to the effect on the molecules of neutral endopeptidase, however, both methods contribute to the elimination of natriuretic peptides.
Receptor system
All the effects of natriuretic peptides are due to their interaction with receptors located in the brain, blood vessels, muscles, bone and adipose tissue. Equivalent to the three types of NUP, there are three types of receptors - A, B and C. But the distribution of "duties" is not so obvious:
- type A receptors interact with atrial and cerebral NUP;
- B-type reacts only to urodilatin;- C receptors can bind to all three types of molecules.
Receptors are fundamentally different from each other. A- and B-types are designed to realize the intracellular effects of the natriuretic peptide, and type C receptors are necessary for the biodegradation of protein molecules. There is an assumption that the effect of the brain NLP is carried out not only through type A receptors, but also with other perceiving sites that respond to the amount of cyclic guanosine monophosphate.
The largest number of type C receptors was found in the tissues of the brain, adrenal glands, kidneys and blood vessels. When a NUP molecule binds to a type C receptor, it is taken up by the cell and cleaved, and the free receptor returns to the membrane.
Physiology of natriuretic peptide
Brain and atrial natriuretic peptides realize their effects through a system of complex physiological reactions. But they all ultimately lead to the same goal - reducing the preload on the heart. NUP affects the cardiovascular, endocrine, excretory and central nervous systems.
Since these molecules have affinity for different receptors, it is difficult to isolate the effects that certain types of NUPs have on a particular system. In addition, the effect of the peptide depends not so much on its type, but on the location of the receiving receptor.
Atrial natriuretic peptide refers to vasoactive peptides, that is, it directly affects the diameter of blood vessels. But besides this, it is able to stimulate the production of nitric oxide, which also promotes vasodilation. The A- and B-type NUPs have the same effect on all types of vessels in terms of strength and direction, and the C-type significantly dilates only the veins.
Recently, there has been an opinion that NUP should be perceived not only as a vasodilator, but mainly as an antagonist of vasoconstrictors. In addition, there are studies that prove that natriuretic peptides affect the distribution of fluid inside and outside the capillary network.
Renal effects of natriuretic peptide
About natriuretic peptide, we can say that it is a diuresis stimulator. Primarily NUP type A enhances renal blood flow andincreases pressure in the vessels of the glomeruli. This, in turn, increases glomerular filtration. At the same time, type C NUPs increase the excretion of sodium ions, and this leads to even more water loss.
With all this, no significant change in systemic pressure is observed, even if the level of peptides is increased several times. All scientists agree that the effects that natriuretic peptides have on the kidneys are necessary to correct the water and electrolyte balance in chronic pathologies of the cardiovascular system.
Effect on the central nervous system
Brain natriuretic peptide, like atrial peptide, cannot cross the blood-brain barrier. Therefore, they act on the structures of the nervous system located outside it. But at the same time, some part of the NUP is secreted by the membranes of the brain and its other parts.
The central effects of natriuretic peptides are that they enhance already existing peripheral changes. So, for example, along with a decrease in the preload on the heart, the body reduces its need for water and mineral s alts, and the tone of the autonomic nervous system changes towards its parasympathetic part.
Laboratory markers
The idea to take natriuretic peptide for analysis during disorders of the cardiovascular system arose in the early 90s of the last century. A decade later, the first publications appeared with the results of research in this area. Type B LPU has been reported to be informative in assessing the degreethe severity of heart failure and predicting the course of the disease.
Protein content is determined in whole venous blood mixed with ethylenediaminetetraacetic acid, or by immunochemical analysis. Normally, the level of NUP should not exceed 100 ng / ml. In addition, the level of NUP precursor can be determined using the electrochemiluminescent method. Domestic medicine, not having such a variety, uses enzyme immunoassay as a universal tool for determining the amount of a substance in blood serum.
Determination of cardiac dysfunction
Natriuretic peptide (normal - up to 100 ng / ml) is currently the most popular and most modern marker for determining cardiac muscle dysfunction. The first studies of peptides were associated with difficulties in differentiating between chronic circulatory failure and chronic obstructive pulmonary disease. Since the clinical symptoms were similar, the test helped to identify the cause of the ailment and predict the further development of the disease.
The second pathology, which was studied from this angle, was coronary heart disease. The authors of the studies agree that the determination of the level of NUP helps to establish the expected level of mortality or relapse in a patient. In addition, dynamic tracking of NLP levels is a marker of treatment effectiveness.
Currently, the level of NUP is determined in patients with cardiomyopathy, hypertension, stenosis of the main vessels andother circulatory disorders.
Application in cardiac surgery
Empirically, it was found that the level of atrial natriuretic peptide in the blood can be considered as an indicator of the severity of the condition and work of the left ventricle in patients before and after heart surgery.
The study of this phenomenon began in 1993, but reached a large scale only in the 2000s. It was found that a sharp decrease in the amount of NUP in the peripheral blood, if before that its level was constantly elevated, indicates that myocardial function is being restored and the operation was successful. If there was no decrease in NUP, then the patient died with a 100% probability. The relationship between age, gender and peptide level has not been identified, therefore, this indicator is universal for all categories of patients.
Prognosis after surgery
Natururetic peptide is elevated before heart surgery. After all, if it were otherwise, then there would be no need for treatment either. A high level of NUP in patients before treatment is an unfavorable factor that greatly affects the prognosis after surgery.
Because the group selected for the study was small, the results were mixed. On the one hand, determining the level of NUP before and after surgery allowed doctors to predict what kind of medical and instrumental support the heart would need until its functions were fully restored. It has also been observed that an increased amountNUP type B is a precursor to atrial fibrillation in the postoperative period.