Natriuretic peptides in the blood

Sodium uretic peptides are important in regulating the volume of sodium and water. The first was the atrial natriuretic peptide (ANP), or the atrial natriuretic peptide type A. The atrial natriuretic peptide, a peptide consisting of 28 amino acid residues, is synthesized and stored in the form of prohormone (126 amino acid residues) in the cardiocytes of the right and left atria degree in the ventricles of the heart) is secreted as an inactive dimer, which is converted into an active monomer in the blood plasma. The main factors regulating the secretion of the atrial natriuretic peptide are an increased volume of circulating blood and an increased central venous pressure. Among other regulatory factors, it should be noted high blood pressure, increased plasma osmolarity, increased heart rate and increased concentration of catecholamines in the blood. Glucocorticosteroids also increase the synthesis of the atrial natriuretic peptide, affecting the atrial natriuretic peptide gene. The primary target for the atrial natriuretic peptide is the kidney, but it also acts on the peripheral arteries. In the kidneys, the atrial natriuretic peptide increases the pressure in the glomerulus, that is, increases the filtration pressure. The atrial natriuretic peptide is capable in itself of enhancing filtration, even if the intra-llular pressure does not change. This leads to an increase in sodium excretion (sodium naresis) along with a large amount of primary urine. The increase in sodium excretion is further due to the suppression of the renal natriuretic peptide secretion of renin by the juxtaglomerular apparatus. Inhibition of the renin-angiotensin-aldosterone system promotes increased sodium excretion and peripheral vasodilation. Additionally, the excretion of sodium is enhanced by the direct action of the atrial natriuretic peptide on the proximal tubules of the nephron and indirect inhibition of the synthesis and secretion of aldosterone. Finally, the atrial natriuretic peptide inhibits the secretion of the atrial natriuretic peptide from the posterior lobe of the pituitary gland. All these mechanisms are ultimately aimed at bringing back to normal the increased amount of sodium and the volume of water in the body and lowering blood pressure. Factors that activate the atrial natriuretic peptide are the opposite of those that stimulate the formation of angiotensin II.

On the plasma membrane of target cells, there is a receptor to the atrial natriuretic peptide. Its binding site is in the extracellular space. The intracellular portion of the ANP receptor is strongly phosphorylated in an inactive form. Once the atrial natriuretic peptide is attached to the extracellular portion of the receptor, activation of guanylate cyclase occurs, which catalyzes the formation of cGMP. In glomerular cells of the adrenal glands, cGMP inhibits the synthesis of aldosterone and its secretion into the blood. In target cells of kidneys and vessels, activation of cGMP leads to the phosphorylation of intracellular proteins, which mediate the biological effects of the atrial natriuretic peptide in these tissues.

In the blood plasma, the atrial natriuretic peptide is in the form of several forms of prohormone. Existing diagnostic systems are based on the ability to determine the concentration of the C-terminal peptide pro-ANP with 99-126 amino acid residues (a-ANP) or two forms with the N-terminal peptide - pro-ANP with 31-67 amino acid residues, and pro-ANP c 78-98 amino acid residues. The reference plasma concentrations for a-ANP are 8.5 ± 1.1 pmol / L (half-life of 3 min), N-pro-ANP with 31-67 amino acid residues - 143.0 + 16.0 pmol / l (half-life of 1-2 hours), N-pro-ANP with 78-98 amino acid residues - 587 + 83 pmol / l. It is believed that pro-ANP with the N-terminal peptide is more stable in the blood, therefore, its study is preferable for clinical purposes. A high concentration of ANP can play a role in reducing the retention of sodium by the kidneys. The atrial natriuretic peptide influences the sympathetic and parasympathetic systems, the renal tubules and the vascular wall.

A number of structurally similar but genetically diverse hormones of the family of natriuretic peptides that are involved in maintaining homeostasis of sodium and water are described. In addition to the atrial natriuretic peptide type A, the brain natriuretic peptide type B (first derived from the bull's brain) and natriuretic peptide type C (composed of 22 amino acids) is of clinical importance. Brain natriuretic peptide type B is synthesized in the myocardium of the right ventricle in the form of a prohormone - a sodium natriuretic peptide peptide, and type C in the brain tissue and vascular endothelium. Each of these peptides is a product of the expression of a single gene. The regulation of secretion and the mechanism of action of the natriuretic peptide type B brain is similar to the atrial natriuretic peptide. Atrial natriuretic peptide and natriuretic peptide type B exert a wide spectrum of action for many tissues, and type C appears to exert only a local effect.

In recent years, atrial natriuretic peptide and brain natriuretic peptide type B are considered as potential markers for assessing the functional state of the contractile ability of the cardiac muscle (a marker of heart failure) and the most important prognostic indicators of the outcome of heart disease.

The concentration of the atrial natriuretic peptide in the blood plasma is increased in patients with congestive heart failure, edema, acute renal failure, chronic renal failure, with cirrhosis of the liver with ascites. In patients in the subacute phase of myocardial infarction, the concentration of natriuretic peptides in blood plasma serves as the best marker for the diagnosis of heart failure and has prognostic significance in terms of the outcome of the disease and death. The increased level of the atrial natriuretic peptide in the blood in most cases correlates with the severity of heart failure. A high sensitivity and specificity of natriuretic peptide type B with respect to the diagnosis of heart failure of any etiology was found independent of the ejection fraction.

The greatest prospect in the diagnosis of heart failure is the study in the blood of the concentration of the brain natriuretic peptide type B, as well as the N-terminal pro-brain natriuretic peptide. This is due to the fact that the B type of natriuretic peptides is secreted by the ventricles of the heart and directly reflects the load on the myocardium, while the atrial natriuretic peptide is synthesized in the atria, therefore it is an "indirect" marker. Atrial fibrillation, the content of the atrial natriuretic peptide decreases over time, reflecting a decrease in the secretory activity of the atria. In addition, the atrial natriuretic peptide is less stable in plasma compared to the brain natriuretic peptide of type B.

The content of natriuretic peptide type B in the blood plasma of patients with heart failure correlates with tolerance to loads and is of greater importance in determining the survival of patients. In this connection, several authors suggest using the determination of the concentration of natriuretic peptide type B as the "gold standard" of diastolic myocardial insufficiency. In the recommendations for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology (2001), the concentration of natriuretic peptides in serum is recommended as a criterion for diagnosing the disease.

The presence of heart failure can be excluded in 98% of cases with the concentration of the atrial natriuretic peptide below 18.1 pmol / l (62.6 pg / ml) and natriuretic peptide type B - below 22.2 pmol / l (76.8 pg / ml). Values above 80 pmol / L are used as the separation point for diagnosis of heart failure for the N-terminal nasal uretic peptide peptide.

The dynamics of the concentration of natriuretic peptides in the blood is a good indicator for evaluating the therapy (the level of the natriuretic peptide of type B can be titrated with a dose of ACE inhibitors) and monitoring the course of the disease in patients with heart failure.

[1], [2], [3], [4], [5], [6]