Brain natriuretic Peptide (BNP)
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Brain natriuretic peptide (BNP), also known as B-type natriuretic peptide and cerebral natriuretic peptide, is another member of the natriuretic peptide system after atrial natriuretic peptide (ANP). Because it was first isolated from the pig brain in 1988 by Japan scholar Sudoh, it actually comes mainly from the ventricles. Like ANP, BNP has a circular structure consisting of 17 amino acids through a pair of disulfide bonds, which are required for receptor binding, where disulfide bonds are important for the biological activity of BNP.
BNPs show specificity in different species. The BNPs of the rat, for example, contains 45 amino acids, while the BNPs of pigs, dogs, and humans contain 32 amino acids. The human BNP gene fragment is located distal to the short arm of chromosome 1 and is linked to the upstream ANP fragment. Its reverse transcription of deoxyribonucleic acid (cDNA) is made up of 1,900 nucleotides, and the messenger ribonucleic acid (mRNA) of BNP is composed of 900 to 1,000 nucleotides and can be expressed as BNP precursors. The N-terminal signal peptide becomes (proBNP), a BNP precursor containing 108 amino acids, but is not stored in secretory granules, but is secreted mainly from the ventricles. During its secretion or after entering the bloodstream, it breaks down into biologically active BNPs (C-terminal fragments containing 32 amino acids) and N-terminal fragments. The release of BNP is regulated by left ventricular stretch and wall tension.
Mechanism of BNP
Brain natriuretic peptide (BNP) plays a crucial role in cardiovascular physiology and pathology. BNP exerts its biological effects through several complex mechanisms. First, BNP acts as a diuretic and natriuretic by promoting sodium excretion and increased urine output, which is essential for maintaining fluid balance and volume regulation. In addition, BNP has a significant vasodilatory effect, and it is able to resist vasoconstriction caused by the renin-angiotensin-aldosterone system (RAAS). This dual effect makes BNP the primary endocrine system against volume overload and hypertension, working in tandem with atrial natriuretic peptide (ANP).
In the case of cardiac insufficiency, the heart is stressed or damaged, which greatly activates the natriuretic peptide system, especially the secretion of BNP. Ventricular load increases, cardiomyocyte stress response, synthesis and release of BNP are significantly increased. Normally, ventricular cardiomyocytes secrete only a small amount of BNP. However, when the heart is damaged or the load increases, such as congestive heart failure, myocardial infarction, ventricular hypertrophy, etc., the secretion of BNP increases dramatically and becomes part of the cardiac compensatory mechanism.
The physiological effects of BNP are mainly achieved by binding to three receptors: NPR-A, NPR-B, and NPR-C. Activation of NPR-A and NPR-B receptors can lead to increased levels of intracellular cyclic guanylate (cGMP), which acts as a second messenger and elicits a variety of physiological effects, including diuretic, natriuretic, vasodilation, and others. In addition, cGMP can also inhibit the activity of the RAAS system, reduce the production of angiotensin II and aldosterone, thereby reducing vascular resistance and blood pressure, and reducing the burden on the heart.
Brain natriuretic peptide function
BNP and ANP function physiologically as natural antagonists of the renin-angiotensin-aldosterone system (RAAS), effectively regulating the activity of the system. They also resist vasopressin and sympathetic effects on sodium and water retention, as well as hypertension. Brain natriuretic peptide was first discovered in brain tissue, but it is mainly secreted by the ventricles. The synthesis and secretion of BNP is mainly stimulated by the increased workload of the ventricles, so its levels can reflect the pressure and expansion of the ventricles. Key features of BNP include:
Lowers blood pressure: BNP lowers blood pressure by dilating blood vessels and inhibiting vasoconstriction. This effect is similar to that of ANP, but the role of BNP is more significant.
Promotes sodium excretion: BNP increases the amount of sodium in the urine, reducing blood volume by reducing fluid accumulation.
Reduce the burden on the heart: BNP can reduce the pressure on the ventricles, thereby reducing the burden on the heart, and has a significant improvement effect on the symptoms of patients with heart failure.
Clinical application of BNP
Detection in patients with heart failure
It is difficult to diagnose patients with heart failure early with traditional detection methods, and BNP is of considerable value in the screening of patients with asymptomatic heart failure. As the severity of heart failure increases, BNP levels gradually increase.
A large number of recent studies have confirmed that BNP levels play an important role as markers in assessing the prognosis and risk stratification of heart failure. High levels of BNP are often seen as an indicator of a poor prognosis. Aggressive treatment of patients with high-risk HF with high BNP levels improves prognosis. For patients with high BNP levels and no significant reduction in BNP levels after adequate anti-heart failure therapy, more aggressive treatment, such as the use of cardiac assist devices, should be considered, and plasma BNP levels are also significantly reduced due to the improvement of cardiac function by cardiac assist devices.
Left ventricular function test
At present, clinical research on BNP is mainly focused on left ventricular dysfunction (LVD), where left ventricular function refers to systolic function. In both normal and left ventricular failure patients, BNP is synthesized and secreted by left ventricular myocytes, then returns to the ventricular septal vein, and enters the circulation through the coronary sinus, and its secretion is mainly regulated by left ventricular wall tension. The severity of LVD is positively correlated with its secretion. The level of BNP in the peripheral blood can reflect the ventricular secretion rate and the degree of LVD.
Brain natriuretic peptide test
Normal value of BNP and its significance
A normal reference value for brain natriuretic peptide (BNP) is 0-100 pg/mL. Clinically, when a patient presents with lower extremity edema and a BNP level of less than 100 pg/mL, the possibility of heart failure can be ruled out, and other causes such as edema due to chronic nephritis should be considered. When BNP>100 pg/mL and accompanied by symptoms such as dyspnea or paroxysmal nocturnal dyspnea, the likelihood of left heart failure is high.
Clinical testing of BNP
The accuracy of BNP testing is critical for the diagnosis of heart failure. Currently, the use of ethylenediaminetetraacetic acid (EDTA) anticoagulant blood collection tubes is clinically required to collect blood samples to prevent degradation or inactivation of BNP in the blood. In addition, since the half-life of BNP in vivo and in vitro is only 20 minutes, it is important to test as soon as possible after blood collection to ensure the reliability and accuracy of the test results. This time constraint emphasizes the efficiency of laboratory operations and the stringent requirements for testing equipment and staffing.
Lab testing for BNP
In the laboratory, there are various methods for the detection of BNP, and commonly used techniques include radioimmunoassay, chemiluminescence, and electrochemiluminescence. Radioimmunoassay (RIA), which uses radiolabeled antibodies to bind specifically to BNP for quantitative detection, has high sensitivity, but has been gradually replaced by other methods due to the use of radioactive materials. Chemiluminescence (CLIA) and electrochemiluminescence (ECLIA) are the most widely used methods, both of which use the principle of photochemical reactions, which not only improve the sensitivity in the detection process, but also shorten the detection time, and the operation is simple and the results are reliable. In conclusion, the detection of BNP level has important guiding significance for the diagnosis and treatment of heart failure, and is one of the important indicators for clinical evaluation of cardiac function.
References
- Mukoyama, Masashi, et al., Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. The Journal of clinical investigation 87.4 (1991): 1402-1412.
- Calzetta, Luigino, et al., Brain natriuretic peptide: much more than a biomarker. International journal of cardiology 221 (2016): 1031-1038.
