What are natriuretic peptides?

As it was explained in the recent past, besides the obvious functions the heart performs also the role of the body of internal secretion. This caused interest not only among theorists from medicine, but also among practitioners. Natriuretic peptides (NUP) are isolated not only in the myocardium, but also in a number of other internal organs that have not previously discredited themselves with endocrine functions. A collective decision was made to use the quantitative indices of NUP in 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 in the eighties of the last century, when scientists saw a connection between the expansion of the chambers of the heart and the intensity of urinary secretion. The authors of the discovery at first considered this phenomenon reflexive 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 proved that the extract from the atria of rats produces a powerful diuretic effect. Then it was possible to isolate the peptide and establish the sequence of amino acid residues constituting it.

Some time later, biochemists isolated three separate components (alpha, beta and gamma) in this protein, not only in chemical structure, but also in terms of the effects: alpha was stronger than the other two. Currently distinguish:

- Atrial NUP (type A);
- brain NUP (type B);
- urodilatin (type C).

Biochemistry of natriuretic peptide

All natriuretic peptides are similar in structure and differ only in terminal nitrogenous radicals or in the arrangement of carbon atoms. To date, all the attention of chemists is concentrated on BUP type B, since it has a more stable form in blood plasma, and also allows obtaining more informative results. The atrial NUP plays the role of one of the correctors of the water-electrolyte balance of the body. It is produced in the myocardium both in norm and in the background of chronic heart failure.

It is proved that the precursor of the brain NUP consists of 108 amino acid residues synthesized by the cells of the left ventricle. When a molecule is loosened from the cytoplasm, it is acted upon by the enzyme furin, which turns 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 ischemia of the heart.

The elimination of NPP from the plasma is carried out in two main ways:

- cleavage with lysosomal enzymes;
- proteolysis.

The leading role is assigned to the effect on neutral endopeptidase molecules, but both methods contribute to the elimination of natriuretic peptides.

Receptor system

All the effects of natriuretic peptides are realized due to their interaction with receptors located in the brain, blood vessels, muscles, bone and adipose tissue. Equivalent to the three types of NPM, there are three types of receptors - A, B and C. But the distribution of "responsibilities" is not so obvious:

- Type A receptors interact with the atrial and cerebral NUP;
- B-type reacts only to urodilatin;
- The receptors C can bind to all three types of molecules.

Receptors are fundamentally different from each other. The A and B types are intended for the realization of the intracellular effects of the natriuretic peptide, and the type C receptors are necessary for the biodegradation of protein molecules. There is an assumption that the effect of brain NUP occurs not only through receptors of type A, but also with other receptor sites that react to the amount of cyclic guanosine monophosphate.

The greatest number of receptors of type C were found in the tissues of the brain, adrenal glands, kidneys and vessels. When the HM molecule binds to the type C receptor, it is absorbed by the cell and cleaved, and the free receptor is returned to the membrane.

Physiology of the natriuretic peptide

Brain and atrial natriuretic peptides realize their effects through a system of complex physiological reactions. But all of them eventually lead to one goal - reducing preload on the heart. NUP affects the cardiovascular, endocrine, excretory and central nervous system.

Since these molecules have an affinity for different receptors, it is difficult to distinguish the effects that certain types of NPM have on a particular system. In addition, the action of the peptide depends not so much on its type as on the location of the receptor receptor.

Atrial natriuretic peptide refers to vasoactive peptides, that is, directly affects the diameter of the vessels. But in addition, it is able to stimulate the production of nitric oxide, which also contributes to the expansion of blood vessels. NPA A and B type have the same strength and directivity effect on all types of vessels, and the C-type largely extends only the veins.

Recently, the opinion is expressed that NPM should be perceived not only as a vasodilator, but primarily as a vasoconstrictor antagonist. 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 the natriuretic peptide, you can say that it is a stimulant diuresis. First of all, type A NP improves renal blood flow and increases the pressure in the glomerular vessels. This, in turn, increases glomerular filtration. At the same time, NPC type C enhances the elimination of sodium ions, and this leads to an even greater loss of water.

However, there is no significant change in systemic pressure, 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-electrolyte balance in chronic pathologies of the cardiovascular system.

Influence on the central nervous system

The brain natriuretic peptide, like the atrial, can not penetrate the blood-brain barrier. Therefore, they affect the structures of the nervous system located outside it. But at the same time some part of NUP is secreted by the brain envelopes and other parts of the brain.

The central effects of natriuretic peptides are that they strengthen the already existing peripheral changes. So, for example, together with the decrease in preload on the heart, the body reduces its need for water and mineral salts, and also changes the tone of the autonomic nervous system toward the parasympathetic part.

Laboratory markers

The idea to take the natriuretic peptide for analysis during cardiovascular disorders occurred in the early 90s of the last century. After a decade, the first publications appeared with the results of research in this field. It was reported that the BH type B is informative in assessing the severity of heart failure and predicting the course of the disease.

The protein content is determined in whole venous blood mixed with ethylenediaminetetraacetic acid, or by immunochemical analysis. Normally, the level of NPC should not exceed 100 ng / ml. In addition, it is possible to determine the level of the NPC precursor by the electrochemiluminescent method. Domestic medicine, not having such a variety, uses the enzyme immunoassay as a universal tool for determining the amount of substance in the blood serum.

Definition of cardiac dysfunction

Sodium-urethritic peptide (norm - up to 100 ng / ml) is currently the most popular and the most modern marker for determining heart muscle dysfunction. The first studies of peptides were associated with difficulties in differentiating 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 examined from this perspective, was coronary heart disease. The authors of the studies agree that the determination of the level of NPM helps to establish the estimated mortality or relapse in the patient. In addition, dynamic monitoring of the level of NUP is a marker of the effectiveness of treatment.

Currently, the level of NUP is determined in patients with cardiomyopathy, hypertension, stenosis of major vessels and other circulatory disorders.

Application in cardiosurgery

Empirically, it was found that the level of the 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 operations.

The study of this phenomenon began as early as 1993, but reached a large scale only in the 2000s. It was found that a sharp decrease in the number of NUP in the peripheral blood, if before this level was constantly elevated, indicates that myocardial function is restored and the operation was successful. If there was no decrease in NUP, the patient died with 100% probability. Interrelations between age, sex and peptide level were not revealed, hence, this indicator is universal for all categories of patients.

Postoperative prognosis

Prior to surgical intervention on the heart, natriuretic peptide is elevated. After all, if it were otherwise, then there was no need for treatment either. A high level of NPM in patients before treatment is an unfavorable factor that strongly affects the prognosis after surgery.

Since the group selected for the study was not numerous, the results were mixed. On the one hand, the determination of the level of the NUP before and after the operation allowed doctors to predict what medication and instrumental support the heart would need until the restoration of its functions. It was also observed that an increased number of type B BCD is a harbinger of atrial fibrillation in the postoperative period.