Жүрек гормонының бүйрек арқылы натрий шығаруын күшейтуі

Cardiac hormone which increases renal sodium excretion

Atrial Natriuretic Peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/paracrine factors that are structurally related. ANP carries out endocrine functions of the heart. It acts as a diuretic by inhibiting sodium reabsorption in the kidneys. ANP also acts in the heart to prevent cardiac hypertrophy and to regulate vascular remodeling and energy metabolism. NPPA expression is varied throughout mammalian development into adulthood. Fetal expression of NPPA is associated with the formation of chamber myocardium, muscle cells of the atria and ventricles in the early developing heart. Early expression of this gene has been associated with ventricular hypertrophy in both in vitro and in vivo models. NPPA variants affect plasma ANP concentrations, blood pressure levels, and cardiovascular diseases such as atrial fibrillation (AF). ANP deficient mice were found to have a large increase in heart and left ventricular weight in response to volume overload, which is normally prevented by proper regulation of blood pressure. Using a knock in (KI) rat model, researchers found an AF associated human variant in NPPA caused inflammation, fibroblast activation, atrial fibrosis, and AF in KI rats. These findings suggest NPPA is a critical gene in cardiac development and dysfunction of this gene can lead to heart problems via altered ANP levels.

The discovery of a natriuretic factor (one that promotes kidney excretion of salt and water) was first reported by Adolfo José de Bold in 1981 when rat atrial extracts were found to contain a substance that increased salt and urine output in the kidney. Later, the substance was purified from heart tissue by several groups and named atrial natriuretic factor (ANF) or ANP.

ANP is a 28 amino acid peptide with a 17 amino acid ring in the middle of the molecule. The ring is formed by a disulfide bond between two cysteine residues at positions 7 and 23. ANP is closely related to BNP (brain natriuretic peptide) and CNP (C type natriuretic peptide), which all share a similar amino acid ring structure. ANP is one of a family of nine structurally similar natriuretic hormones: seven are atrial in origin.

Maintenance of the ECF volume (space), and its subcompartment the vascular space, is crucial for survival. These compartments are maintained within a narrow range, despite wide variations in dietary sodium intake. There are three volume regulating systems: two salt saving systems, the renin angiotensin aldosterone system (RAAS) and the renal sympathetic system (RSS); and the salt excreting natriuretic peptide (NP) hormone system. When the vascular space contracts, the RAAS and RSS are "turned on"; when the atria expand, NP's are "turned on". Each system also suppresses its counteracting system(s). NP's are made in cardiac, intestinal, renal, and adrenal tissue: ANP in one of a family of cardiac NP's: others at BNP, CNP, and DNP. The medullary collecting duct is the main site of ANP regulation of sodium excretion. ANP directly dilates the afferent arteriole and counteracts the norepinephrine induced vasoconstriction of the afferent arteriole. Some studies suggest that ANP also constricts the efferent arteriole, but this is not a unanimous finding.

ANP inhibits cardiac hypertrophy in heart failure as well as fibrosis. Fibrosis is inhibited by preventing fibroblasts from entering heart tissue and replicating, as well as decreasing inflammation. ANP modulates innate immunity by raising defence against extracellular microbes and inhibiting the release of pro inflammatory markers and expression of adhesion molecules. ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, coronary artery disease, myocardial infarction and heart failure. A specific ANP precursor called mid regional pro atrial natriuretic peptide (MRproANP) is a highly sensitive biomarker in heart failure. MRproANP levels below 120 pmol/L can be used to effectively rule out acute heart failure.

Opinions regarding the use of ANP for the treatment of acute heart failure and kidney disease are varied. While this molecule has been shown to successfully restore some hemodynamic parameters following heart failure, and yield clinical improvement for kidney injury, whether it ultimately reduces mortality and its long term effects are unknown. Therefore, more studies need to be conducted to better understand the therapeutic effects of ANP. Preliminary research on one of such molecules, ularitide, has shown that this drug is safe, well tolerated, and effective in the treatment of acute heart failure. and dendroaspis natriuretic peptide (DNP) has been found in the venom of the green mamba, as well as an NP in a species of African snake. Beside these four, five additional natriuretic peptides have been identified: long acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide, urodilatin, and adrenomedullin. Omapatrilat (dual inhibitor of NEP and angiotensin converting enzyme) developed by BMS did not receive FDA approval due to angioedema safety concerns. Other dual inhibitors of NEP with ACE/angiotensin receptor are (in 2003) being developed by pharmaceutical companies.

ANP is also called atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), cardionatrine, cardiodilatin (CDD), and atriopeptin.