scholarly journals Molecular Signaling Mechanisms and Function of Natriuretic Peptide Receptor-A in the Pathophysiology of Cardiovascular Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kailash N. Pandey
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Natriuretic Peptides ◽  
Molecular Genetic ◽  
Natriuretic Peptide Receptor ◽  
Functional Roles ◽  
Peptide Receptor ◽  
Signaling Mechanisms ◽  
Natriuretic Peptide Receptor A ◽  
Cardiovascular Homeostasis

The discovery of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) and their cognate receptors has greatly increased our knowledge of the control of hypertension and cardiovascular homeostasis. ANP and BNP are potent endogenous hypotensive hormones that elicit natriuretic, diuretic, vasorelaxant, antihypertrophic, antiproliferative, and antiinflammatory effects, largely directed toward the reduction of blood pressure (BP) and cardiovascular diseases (CVDs). The principal receptor involved in the regulatory actions of ANP and BNP is guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), which produces the intracellular second messenger cGMP. Cellular, biochemical, molecular, genetic, and clinical studies have facilitated understanding of the functional roles of natriuretic peptides (NPs), as well as the functions of their receptors, and signaling mechanisms in CVDs. Transgenic and gene-targeting (gene-knockout and gene-duplication) strategies have produced genetically altered novel mouse models and have advanced our knowledge of the importance of NPs and their receptors at physiological and pathophysiological levels in both normal and disease states. The current review describes the past and recent research on the cellular, molecular, genetic mechanisms and functional roles of the ANP-BNP/NPRA system in the physiology and pathophysiology of cardiovascular homeostasis as well as clinical and diagnostic markers of cardiac disorders and heart failure. However, the therapeutic potentials of NPs and their receptors for the diagnosis and treatment of cardiovascular diseases, including hypertension, heart failure, and stroke have just begun to be expanded. More in-depth investigations are needed in this field to extend the therapeutic use of NPs and their receptors to treat and prevent CVDs.

scholarly journals Molecular and genetic aspects of guanylyl cyclase natriuretic peptide receptor-A in regulation of blood pressure and renal function

2018 ◽  
Vol 50 (11) ◽  
pp. 913-928 ◽  
Author(s):  
Kailash N. Pandey
Keyword(s):  
Blood Pressure ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Molecular Mechanisms ◽  
Phenotypic Characterization ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Regulation Of Blood Pressure

Natriuretic peptides (NPs) exert diverse effects on several biological and physiological systems, such as kidney function, neural and endocrine signaling, energy metabolism, and cardiovascular function, playing pivotal roles in the regulation of blood pressure (BP) and cardiac and vascular homeostasis. NPs are collectively known as anti-hypertensive hormones and their main functions are directed toward eliciting natriuretic/diuretic, vasorelaxant, anti-proliferative, anti-inflammatory, and anti-hypertrophic effects, thereby, regulating the fluid volume, BP, and renal and cardiovascular conditions. Interactions of NPs with their cognate receptors display a central role in all aspects of cellular, biochemical, and molecular mechanisms that govern physiology and pathophysiology of BP and cardiovascular events. Among the NPs atrial and brain natriuretic peptides (ANP and BNP) activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and initiate intracellular signaling. The genetic disruption of Npr1 (encoding GC-A/NPRA) in mice exhibits high BP and hypertensive heart disease that is seen in untreated hypertensive subjects, including high BP and heart failure. There has been a surge of interest in the NPs and their receptors and a wealth of information have emerged in the last four decades, including molecular structure, signaling mechanisms, altered phenotypic characterization of transgenic and gene-targeted animal models, and genetic analyses in humans. The major goal of the present review is to emphasize and summarize the critical findings and recent discoveries regarding the molecular and genetic regulation of NPs, physiological metabolic functions, and the signaling of receptor GC-A/NPRA with emphasis on the BP regulation and renal and cardiovascular disorders.

The renal and cardiovascular effects of natriuretic peptides

2017 ◽  
Vol 41 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Philip Ching Yat Wong ◽  
Jun Guo ◽  
Aidong Zhang
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Cardiovascular Effects ◽  
Target Cells ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Endocrine Organs ◽  
Patients With Heart Failure

The landmark report by de Bold et al. in 1981 signified the heart as one of the endocrine organs involved in fluid and salt balance (de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. Life Sci 28: 89–94, 1981). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from cardiomyocytes in response to cardiac stretch as in the case of heart failure, whereas C-type natriuretic peptide (CNP) is secreted from endothelial and renal cells in response to cytokines and endothelium-dependent agonists, such as acetylcholine. Binding ANP or BNP to natriuretic peptide receptor A induces cyclic guanylyl monophosphate as second messenger in the target cells to mediate the following: natriuresis; water diuresis; increasing glomerular filtration rate; decreasing systemic sympathetic activities; plasma volume; cardiac output and blood pressure; and curbing mitoses of heart fibroblasts and hypertrophy of cardiovascular muscle cells. ANP, BNP, and CNP are cleared from the bloodstream by natriuretic peptide receptor C and degraded by an ectoenzyme called neprilysin (NEP). The plasma levels of BNP are typically >100 pg/ml in patients with congestive heart failure. Sacubitril/valsartan is an angiotensin receptor NEP inhibitor that prevents the clinical progression of surviving patients with heart failure more effectively than enalapril, an angiotensin-converting enzyme inhibitor. A thorough understanding of the renal and cardiovascular effects of natriuretic peptides is of major importance for first-year medical students to gain insight into the significance of plasma levels of BNP in patients with heart failure.

scholarly journals The Importance of Natriuretic Peptides in Cardiometabolic Diseases

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Shravya Vinnakota ◽  
Horng H Chen
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Defense Mechanisms ◽  
Pressure Overload ◽  
Natriuretic Peptide Receptor ◽  
Therapeutic Role ◽  
Peptide Receptor ◽  
Genes Encoding ◽  
Natriuretic Peptide Receptor A

Abstract The natriuretic peptide (NP) system is composed of 3 distinct peptides (atrial natriuretic peptide or ANP, B-type natriuretic peptide or BNP, and C-type natriuretic peptide or CNP) and 3 receptors (natriuretic peptide receptor-A or NPR-A or particulate guanynyl cyclase-A natriuretic peptide receptor-B or NPR-B or particulate guanynyl cyclase-B, and natriuretic peptide receptor-C or NPR-C or clearance receptor). ANP and BNP function as defense mechanisms against ventricular stress and the deleterious effects of volume and pressure overload on the heart. Although the role of NPs in cardiovascular homeostasis has been extensively studied and well established, much remains uncertain about the signaling pathways in pathological states like heart failure, a state of impaired natriuretic peptide function. Elevated levels of ANP and BNP in heart failure correlate with disease severity and have a prognostic value. Synthetic ANP and BNP have been studied for their therapeutic role in hypertension and heart failure, and promising trials are under way. In recent years, the expression of ANP and BNP in human adipocytes has come to light. Through their role in promotion of adipocyte browning, lipolysis, lipid oxidation, and modulation of adipokine secretion, they have emerged as key regulators of energy consumption and metabolism. NPR-A signaling in skeletal muscles and adipocytes is emerging as pivotal to the maintenance of long-term insulin sensitivity, which is disrupted in obesity and reduced glucose-tolerance states. Genetic variants in the genes encoding for ANP and BNP have been associated with a favorable cardiometabolic profile. In this review, we discuss several pathways that have been proposed to explain the role of NPs as endocrine networkers. There is much to be explored about the therapeutic role of NPs in improving metabolic milieu.

scholarly journals Natriuretic Peptides and Analytical Barriers

2017 ◽  
Vol 63 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Vlad C Vasile ◽  
Allan S Jaffe
Keyword(s):  
Heart Failure ◽  
Clinical Practice ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Myocardial Function ◽  
Specific Assay ◽  
Peptide System ◽  
Cardiovascular Homeostasis ◽  
Natriuretic Peptide System

Abstract BACKGROUND The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function. CONTENT Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized. SUMMARY This review presents the relevant issues related to the biology of natriuretic peptides and differences between assays with immediate implications for clinical practice.

Physical Mapping of the Human Connexin 40 (GJA5), Flavin-Containing Monooxygenase 5, and Natriuretic Peptide Receptor A Genes on 1q21

Genomics ◽  
1997 ◽  
Vol 39 (3) ◽  
pp. 409-411 ◽  
Author(s):  
Bruce D. Gelb ◽  
Jian Zhang ◽  
Philip D. Cotter ◽  
Irina F. Gershin ◽  
Robert J. Desnick
Keyword(s):  
Natriuretic Peptide ◽  
Physical Mapping ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Connexin 40 ◽  
Natriuretic Peptide Receptor A
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