Blood natriuretic peptides

Natriuretic peptides play an important role in the regulation of sodium and water volume. The first to be discovered was atrial natriuretic peptide (ANP), or atrial natriuretic peptide type A. Atrial natriuretic peptide is a peptide consisting of 28 amino acid residues, synthesized and stored as a prohormone (126 amino acid residues) in the cardiocytes of the right and left atrium (to a much lesser extent in the ventricles of the heart), secreted as an inactive dimer, which is converted into an active monomer in the blood plasma. The main factors regulating the secretion of atrial natriuretic peptide are increased circulating blood volume and increased central venous pressure. Among other regulatory factors, it is necessary to note high blood pressure, increased plasma osmolarity, increased heart rate and increased concentration of catecholamines in the blood. Glucocorticosteroids also increase the synthesis of atrial natriuretic peptide by influencing the atrial natriuretic peptide gene. The primary target of atrial natriuretic peptide is the kidneys, but it also acts on the peripheral arteries. In the kidneys, atrial natriuretic peptide increases intraglomerular pressure, i.e. increases filtration pressure. atrial natriuretic peptide itself is capable of enhancing filtration, even if intraglomerular pressure does not change. This leads to increased sodium excretion (natriuresis) along with a larger amount of primary urine. The increase in sodium excretion is additionally caused by atrial natriuretic peptide suppression of renin secretion by the juxtaglomerular apparatus. Inhibition of the renin-angiotensin-aldosterone system promotes increased sodium excretion and peripheral vasodilation. Additionally, sodium excretion is enhanced by the direct action of atrial natriuretic peptide on the proximal tubule of the nephron and by indirect inhibition of aldosterone synthesis and secretion. Finally, atrial natriuretic peptide inhibits the secretion of atrial natriuretic peptide from the posterior pituitary gland. All of these mechanisms ultimately serve to restore the increased sodium and water volume in the body to normal and to reduce blood pressure. The factors that activate atrial natriuretic peptide are the opposite of those that stimulate the formation of angiotensin II.

The plasma membrane of target cells contains a receptor for atrial natriuretic peptide. Its binding site is located in the extracellular space. The intracellular site of the ANP receptor is highly phosphorylated in an inactive form. Once atrial natriuretic peptide binds to the extracellular site of the receptor, guanylate cyclase is activated, catalyzing the formation of cGMP. In adrenal glomerular cells, cGMP inhibits aldosterone synthesis and its secretion into the blood. In renal and vascular target cells, cGMP activation leads to phosphorylation of intracellular proteins that mediate the biological effects of atrial natriuretic peptide in these tissues.

In blood plasma, atrial natriuretic peptide exists in several forms of the prohormone. Existing diagnostic systems are based on the ability to determine the concentration of the C-terminal peptide of 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 with 78-98 amino acid residues. The reference values of concentrations in blood plasma are for a-ANP - 8.5+1.1 pmol/l (half-life 3 min), N-pro-ANP with 31-67 amino acid residues - 143.0+16.0 pmol/l (half-life 1-2 h), N-pro-ANP with 78-98 amino acid residues - 587+83 pmol/l. Pro-ANP with N-terminal peptide is considered to be more stable in blood, so its study is preferable for clinical purposes. High concentration of ANP may play a role in reducing sodium retention by the kidneys. Atrial natriuretic peptide affects the sympathetic and parasympathetic systems, renal tubules and vascular wall.

Currently, a number of structurally similar but genetically different hormones of the natriuretic peptide family have been described, which participate in maintaining sodium and water homeostasis. In addition to atrial natriuretic peptide type A, brain natriuretic peptide type B (first obtained from bovine brain) and natriuretic peptide type C (consists of 22 amino acids) are of clinical significance. Brain natriuretic peptide type B is synthesized in the myocardium of the right ventricle as a prohormone - pro-brain natriuretic peptide, and type C in brain tissue and vascular endothelium. Each of these peptides is a product of expression of a separate gene. Regulation of secretion and mechanism of action of brain natriuretic peptide type B are similar to atrial natriuretic peptide. Atrial natriuretic peptide and B-type natriuretic peptide have a broad spectrum of action in many tissues, while type C appears to have only a local effect.

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

Plasma atrial natriuretic peptide levels are elevated in patients with congestive heart failure, edema, acute renal failure, chronic renal failure, and liver cirrhosis with ascites. In patients in the subacute phase of myocardial infarction, plasma natriuretic peptide levels are the best marker for diagnosing heart failure and have prognostic value for disease outcome and death. Elevated blood atrial natriuretic peptide levels correlate with heart failure severity in most cases. Ejection fraction-independent high sensitivity and specificity of B-type natriuretic peptide for diagnosing heart failure of any etiology have been demonstrated.

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

The content of natriuretic peptide type B in the blood plasma of patients with heart failure correlates with exercise tolerance and is of greater importance in determining the survival of patients. In this regard, a number of 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 the blood serum is recommended to be used as a criterion for diagnosing the disease.

The presence of heart failure can be excluded in 98% of cases with atrial natriuretic peptide concentrations below 18.1 pmol/L (62.6 pg/mL) and B-type natriuretic peptide concentrations below 22.2 pmol/L (76.8 pg/mL). Values above 80 pmol/L are used as a cutoff point for the diagnosis of heart failure for N-terminal pro-brain natriuretic peptide.

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

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