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The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects
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The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 May 2023) | Viewed by 16185

Special Issue Editor

Dr. Vittoriano Della Corte

E-Mail Website
Guest Editor
Internal Medicine and Stroke Care Ward, Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialities (PROMISE) “G. D’Alessandro”, University of Palermo, 90127 Palermo, Italy
Interests: internal medicine; arterial stiffness; endothelial dysfunction; vascular ultrasound; blood gas analysis acid-base equilibrium; stroke; cardiovascular diseases; cardiology; phlebology; atherosclerosis
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Special Issue Information

Dear Colleagues,

The natriuretic peptide family includes a set of polypeptide mediators: the atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Dendroaspis natriuretic peptide (DNP), urodilatin, guanylin, and uroguanylin. Their functions are heterogeneous and influence metabolism in various organs and tissues.

Mainly known for their actions on the cardiovascular system, they exert diuretic and natriuretic action, regulating central fluid volume and blood pressure. This mainly happens thanks to the endocrine functions of ANP and BNP. DNP exhibits similar actions, but its physiological role has not yet been clarified. Furthermore, ANP and BNP have local (autocrine/paracrine) regulatory actions within the heart, and CNP carries out local regulatory actions within the vessel wall. CNP also regulates bone metabolism (a potent stimulator of endochondral bone growth) and is involved in various reproductive processes as well as in embryonic and fetal development. ANP, BNP, and CNP even play a role in the central nervous system, influencing neuronal development, synaptic transmission, and neuroprotection. Guanylin and uroguanylin are synthesized in the intestine and are released both luminally and into circulation. They may act as a hormone in the novel endocrine axis, linking the digestive system and kidney to increase sodium excretion in the postprandial period. Finally, urodilatin is synthesized in the kidney and acts in an autocrine and paracrine way by stimulating diuresis and natriuresis. It is thought to play a greater role in the regulation of blood sodium than ANP and BNP.

In this Special Issue, we look forward to receiving original research and reviews that highlight recent advances in our understanding of natriuretic peptides' function and metabolism both from physiological and pathophysiological perspectives.

Dr. Vittoriano Della Corte
Guest Editor

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Keywords

  • natriuretic peptide family
  • natriuretic peptides
  • atrial natriuretic peptide
  • ANP
  • brain natriuretic peptide
  • BNP
  • C-type natriuretic peptide
  • CNP
  • dendroaspis natriuretic peptide
  • DNP
  • urodilatin
  • guanylin
  • uroguanylin

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Published Papers (5 papers)

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Research

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24 pages, 3278 KiB  
Article
Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development
by Andrew J. Lessey, Samantha M. Mirczuk, Annisa N. Chand, Deborah M. Kurrasch, Márta Korbonits, Stijn J. M. Niessen, Craig A. McArdle, Imelda M. McGonnell and Robert C. Fowkes
Int. J. Mol. Sci. 2023, 24(16), 12921; https://doi.org/10.3390/ijms241612921 - 18 Aug 2023
Cited by 1 | Viewed by 1952
Abstract
Human patients with mutations within NPPC or NPR2 genes (encoding C-type natriuretic peptide (CNP) and guanylyl cyclase-B (GC-B), respectively) display clinical signs associated with skeletal abnormalities, such as overgrowth or short stature. Mice with induced models of Nppc or Npr2 deletion display profound [...] Read more.
Human patients with mutations within NPPC or NPR2 genes (encoding C-type natriuretic peptide (CNP) and guanylyl cyclase-B (GC-B), respectively) display clinical signs associated with skeletal abnormalities, such as overgrowth or short stature. Mice with induced models of Nppc or Npr2 deletion display profound achondroplasia, dwarfism and early death. Recent pharmacological therapies to treat short stature are utilizing long-acting CNP analogues, but the effects of manipulating CNP expression during development remain unknown. Here, we use Danio rerio (zebrafish) as a model for vertebrate development, employing both pharmacological and reverse genetics approaches to alter expression of genes encoding CNP in zebrafish. Four orthologues of CNP were identified in zebrafish, and spatiotemporal expression profiling confirmed their presence during development. Bioinformatic analyses suggested that nppcl is the most likely the orthologue of mammalian CNP. Exogenous CNP treatment of developing zebrafish embryos resulted in impaired growth characteristics, such as body length, head width and eye diameter. This reduced growth was potentially caused by increased apoptosis following CNP treatment. Expression of endogenous nppcl was downregulated in these CNP-treated embryos, suggesting that negative feedback of the CNP system might influence growth during development. CRISPR knock-down of endogenous nppcl in developing zebrafish embryos also resulted in impaired growth characteristics. Collectively, these data suggest that CNP in zebrafish is crucial for normal embryonic development, specifically with regard to growth. Full article
(This article belongs to the Special Issue The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects)
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21 pages, 4404 KiB  
Article
Ligand-Dependent Downregulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Role of miR-128 and miR-195
by Madan L. Khurana, Indra Mani, Prerna Kumar, Chandramohan Ramasamy and Kailash N. Pandey
Int. J. Mol. Sci. 2022, 23(21), 13381; https://doi.org/10.3390/ijms232113381 - 2 Nov 2022
Cited by 4 | Viewed by 2063
Abstract
Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous [...] Read more.
Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in 125I-ANP binding, Guanylyl cyclase (GC) activity of receptor, and intracellular accumulation of cGMP leading to downregulation of NPRA. Treatment with ANP (100 nM) for 12 h led to an 80% decrease in 125I-ANP binding to its receptor, and BNP decreased it by 62%. Neither 100 nM c-ANF (truncated ANF) nor C-type natriuretic peptide (CNP) had any effect. ANP (100 nM) treatment also decreased GC activity by 68% and intracellular accumulation cGMP levels by 45%, while the NPRA antagonist A71915 (1 µM) almost completely blocked ANP-dependent downregulation of NPRA. Treatment with the protein kinase G (PKG) stimulator 8-(4-chlorophenylthio)-cGMP (CPT-cGMP) (1 µM) caused a significant increase in 125I-ANP binding, whereas the PKG inhibitor KT 5823 (1 µM) potentiated the effect of ANP on the downregulation of NPRA. The transfection of miR-128 significantly reduced NPRA protein levels by threefold compared to control cells. These results suggest that ligand-dependent mechanisms play important roles in the downregulation of NPRA in target cells. Full article
(This article belongs to the Special Issue The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects)
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16 pages, 2276 KiB  
Article
Renal Corin Is Essential for Normal Blood Pressure and Sodium Homeostasis
by Tiantian Zhou, Shengnan Zhang, Chunyu Du, Kun Wang, Xiabing Gu, Shijin Sun, Xianrui Zhang, Yayan Niu, Can Wang, Meng Liu, Ningzheng Dong and Qingyu Wu
Int. J. Mol. Sci. 2022, 23(19), 11251; https://doi.org/10.3390/ijms231911251 - 24 Sep 2022
Cited by 9 | Viewed by 1984
Abstract
Atrial natriuretic peptide (ANP)-mediated natriuresis is known as a cardiac endocrine function in sodium and body fluid homeostasis. Corin is a protease essential for ANP activation. Here, we studied the role of renal corin in regulating salt excretion and blood pressure. We created [...] Read more.
Atrial natriuretic peptide (ANP)-mediated natriuresis is known as a cardiac endocrine function in sodium and body fluid homeostasis. Corin is a protease essential for ANP activation. Here, we studied the role of renal corin in regulating salt excretion and blood pressure. We created corin conditional knockout (cKO), in which the Corin gene was selectively disrupted in the kidney (kcKO) or heart (hcKO). We examined the blood pressure, urinary Na+ and Cl− excretion, and cardiac hypertrophy in wild-type, corin global KO, kcKO, and hcKO mice fed normal- and high-salt diets. We found that on a normal-salt diet (0.3% NaCl), corin kcKO and hcKO mice had increased blood pressure, indicating that both renal and cardiac corin is necessary for normal blood pressure in mice. On a high-salt diet (4% NaCl), reduced urinary Na+ and Cl− excretion, increased body weight, salt-exacerbated hypertension, and cardiac hypertrophy were observed in corin kcKO mice. In contrast, impaired urinary Na+ and Cl− excretion and salt-exacerbated hypertension were not observed in corin hcKO mice. These results indicated that renal corin function is important in enhancing natriuresis upon high salt intakes and that this function cannot be compensated by the cardiac corin function in mice. Full article
(This article belongs to the Special Issue The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects)
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Review

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31 pages, 873 KiB  
Review
The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects
by Vittoriano Della Corte, Gaetano Pacinella, Federica Todaro, Rosaria Pecoraro and Antonino Tuttolomondo
Int. J. Mol. Sci. 2023, 24(11), 9642; https://doi.org/10.3390/ijms24119642 - 1 Jun 2023
Cited by 6 | Viewed by 3302
Abstract
In the modern scientific landscape, natriuretic peptides are a complex and interesting network of molecules playing pleiotropic effects on many organs and tissues, ensuring the maintenance of homeostasis mainly in the cardiovascular system and regulating the water–salt balance. The characterization of their receptors, [...] Read more.
In the modern scientific landscape, natriuretic peptides are a complex and interesting network of molecules playing pleiotropic effects on many organs and tissues, ensuring the maintenance of homeostasis mainly in the cardiovascular system and regulating the water–salt balance. The characterization of their receptors, the understanding of the molecular mechanisms through which they exert their action, and the discovery of new peptides in the last period have made it possible to increasingly feature the physiological and pathophysiological role of the members of this family, also allowing to hypothesize the possible settings for using these molecules for therapeutic purposes. This literature review traces the history of the discovery and characterization of the key players among the natriuretic peptides, the scientific trials performed to ascertain their physiological role, and the applications of this knowledge in the clinical field, leaving a glimpse of new and exciting possibilities for their use in the treatment of diseases. Full article
(This article belongs to the Special Issue The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects)
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18 pages, 1046 KiB  
Review
Role of Cardiac Natriuretic Peptides in Heart Structure and Function
by Riccardo Sarzani, Massimiliano Allevi, Chiara Di Pentima, Paola Schiavi, Francesco Spannella and Federico Giulietti
Int. J. Mol. Sci. 2022, 23(22), 14415; https://doi.org/10.3390/ijms232214415 - 20 Nov 2022
Cited by 41 | Viewed by 6171
Abstract
Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP) are true hormones produced and released by cardiomyocytes, exerting several systemic effects. Together with C-type NP (CNP), mainly expressed by endothelial cells, they also exert several paracrine and autocrine activities on the [...] Read more.
Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP) are true hormones produced and released by cardiomyocytes, exerting several systemic effects. Together with C-type NP (CNP), mainly expressed by endothelial cells, they also exert several paracrine and autocrine activities on the heart itself, contributing to cardiovascular (CV) health. In addition to their natriuretic, vasorelaxant, metabolic and antiproliferative systemic properties, NPs prevent cardiac hypertrophy, fibrosis, arrhythmias and cardiomyopathies, counteracting the development and progression of heart failure (HF). Moreover, recent studies revealed that a protein structurally similar to NPs mainly produced by skeletal muscles and osteoblasts called musclin/osteocrin is able to interact with the NPs clearance receptor, attenuating cardiac dysfunction and myocardial fibrosis and promoting heart protection during pathological overload. This narrative review is focused on the direct activities of this molecule family on the heart, reporting both experimental and human studies that are clinically relevant for physicians. Full article
(This article belongs to the Special Issue The Natriuretic Peptide Family: A Single Entity, Pleiotropic Effects)
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