Natriuretic peptides in blood plasma
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 ANP peptide consisting of 28 amino acid residues is synthesized and stored as prohormone( 126 amino acid residues) in the cardiocytes of the right and left auricles(much less 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 ANP are increased volume of circulating blood and increased central venous pressure. Among other regulatory factors, it is necessary to note high blood pressure, increased osmolarity of the plasma, increased heart rate and increased concentration of catecholamines in the blood. HA also increases the synthesis of ANP, affecting the gene ANP.The primary target for ANP is the kidney, but it also acts on the peripheral arteries. In the kidneys, the ANP increases the pressure in the glomerulus, that is, increases the filtration pressure. ANP is able to increase filtration by itself, even if the intra-cell pressure does not change. This leads to an increase in sodium excretion( sodium naresis) along with a large amount of primary urine. Increase
Fig. Effects of the atrial natriuretic peptide
Fig. Effects of the atrial natriuretic peptide
sodium excretion is additionally due to the suppression of ANP secretion of renin by the juxtaglomerular apparatus. The 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 ANP on the proximal tubules of the nephron and indirect inhibition of the synthesis and secretion of aldosterone. Finally, ANP inhibits the secretion of ADH 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 ANP are opposite to those that stimulate the formation of angiotensin II.
The receptor for the ANP is present on the plasma membrane of target cells. Its binding site is in the extracellular space. The intracellular portion of the ANP-receptor is strongly phosphorylated-
is inactive form. Once ANP joins the extra-cellular site 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 phosphorylation of intracellular proteins, which mediate the biological effects of ANP in these tissues.
In the blood plasma, ANP 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 c78-98 amino acid residues [Hunter MEF et al., 1998].The reference values for 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 [Hunter MEF et al., 1998].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. ANP affects 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 prohormone - a sodium natriuretic peptide peptide, and type C in brain tissue and endothelial vascular. 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 ANP.ANP and natriuretic peptide type B have a wide spectrum of action for many tissues, and type C appears to have only a local effect.
In recent years, ANP 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 ANP in the blood plasma is increased in patients with congestive heart failure, edema, arthritis, CPN, with cirrhosis of the liver with ascites. In patients in the subacute phase of MI, 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 ANP in the blood in most cases correlates with the severity of the heart failure
ti. A high sensitivity and specificity of type B natriuretic peptide for detecting heart failure of any etiology was found independent of the ejection fraction [Nakamura M. et al., 2001].
The greatest prospect in the diagnosis of heart failure is the study in the blood of the concentration of the brain natriouretic 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 ANP is synthesized in the atria, therefore it is an "indirect" marker. At the atrial fibrillation, the ANP content decreases with time, reflecting a decrease in the secretory activity of the atria. In addition, the ANP is less stable in plasma than the brain natriuretic peptide type B.
The content of natriuretic peptide type B in the blood plasma of patients with heart failure correlates with tolerance to stress 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 an ANP concentration below 18.1 pmol / l( 62.6 pg / ml) and brain natriuretic peptide type B - below 22.2 pmol / l( 76.8 pg / ml) [Cowie M. et al., 1997].Values above 80 pmol / l are used as the separation point for the diagnosis of heart failure for the N-terminal nasal-uretic peptide peptide [Karl J. et al., 1999].