Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type‐A recapitulated by soluble guanylyl cyclase agonists

2020 ◽  
Author(s):  
Andreas Frees ◽  
Kasper B. Assersen ◽  
Mia Jensen ◽  
Pernille B.L. Hansen ◽  
Paul M. Vanhoutte ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Soluble Guanylyl Cyclase ◽  
Type A ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

Natriuretic Peptide Receptor Type A (NPRA)

2016 ◽  
pp. 1-7
Author(s):  
Natalia L. Rukavina Mikusic ◽  
María I. Rosón ◽  
Nicolás M. Kouyoumdzian ◽  
Silvana M. Cantú ◽  
Belisario E. Fernández ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Type A ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

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.

Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice

2009 ◽  
Vol 297 (6) ◽  
pp. E1339-E1348 ◽  
Author(s):  
Takei Kake ◽  
Hidetomo Kitamura ◽  
Yuichiro Adachi ◽  
Tetsuro Yoshioka ◽  
Tomoyuki Watanabe ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Critical Role ◽  
Skeletal Growth ◽  
Heart Weight ◽  
Receptor Subtype ◽  
Natriuretic Peptide Receptor ◽  
High Concentration ◽  
Peptide Receptor

C-type natriuretic peptide (CNP) plays a critical role in endochondral ossification through guanylyl cyclase-B (GC-B), a natriuretic peptide receptor subtype. Cartilage-specific overexpression of CNP enhances skeletal growth and rescues the dwarfism in a transgenic achondroplasia model with constitutive active mutation of fibroblast growth factor receptor-3. For future clinical application, the efficacy of CNP administration on skeletal growth must be evaluated. Due to the high clearance of CNP, maintaining a high concentration is technically difficult. However, to model high blood CNP concentration, we established a liver-targeted CNP-overexpressing transgenic mouse (SAP-CNP tgm). SAP-CNP tgm exhibited skeletal overgrowth in proportion to the blood CNP concentration and revealed phenotypes of systemic stimulation of cartilage bones, including limbs, paws, costal bones, spine, and skull. Furthermore, in SAP-CNP tgm, the size of the foramen magnum, the insufficient formation of which results in cervico-medullary compression in achondroplasia, also showed significant increase. CNP primarily activates GC-B, but under high concentrations it cross-reacts with guanylyl cyclase-A (GC-A), a natriuretic peptide receptor subtype of atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP). Although activation of GC-A could alter cardiovascular homeostasis, leading to hypotension and heart weight reduction, the skeletal overgrowth phenotype in the line of SAP-CNP tgm with mild overexpression of CNP did not accompany decrease of systolic blood pressure or heart weight. These results suggest that CNP administration stimulates skeletal growth without adverse cardiovascular effect, and thus CNP could be a promising remedy targeting achondroplasia.

Natriuretic Peptide Receptor Type A (NPRA)

2018 ◽  
pp. 3344-3351 ◽  
Author(s):  
Natalia L. Rukavina Mikusic ◽  
María I. Rosón ◽  
Nicolás M. Kouyoumdzian ◽  
Silvana M. Cantú ◽  
Belisario E. Fernández ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Type A ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

Further attenuation of endothelium-dependent relaxation imparted by natriuretic peptide receptor antagonism

1999 ◽  
Vol 277 (4) ◽  
pp. H1618-H1621 ◽  
Author(s):  
Paul W. Wennberg ◽  
Virginia M. Miller ◽  
Ton Rabelink ◽  
John C. Burnett
Keyword(s):  
Endothelial Cells ◽  
Natriuretic Peptide ◽  
Coronary Arteries ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Peptide System ◽  
Endothelium Dependent Relaxation

Nitric oxide (NO) is an important endothelium-derived relaxing factor that functions via activation of soluble guanylyl cyclase and cGMP generation in vascular smooth muscle. Recently, studies have described the synthesis and secretion of C-type natriuretic peptide (CNP) from endothelial cells. This peptide also mediates relaxation via cGMP but through activation of particulate guanylyl cyclase. We tested the hypothesis that endothelium-dependent relaxations to acetylcholine or bradykinin in isolated canine coronary arteries involve both releases of NO and CNP. Rings of canine coronary arteries were incubated with either inhibitors of NO production ( N G-monomethyl-l-arginine,l-NMMA) or the natriuretic peptide receptor antagonist HS-142-1. CNP caused concentration-dependent relaxations of rings with and without endothelium. These relaxations were attenuated by HS-142-1. Relaxations to acetylcholine and bradykinin were attenuated byl-NMMA alone but not attenuated by HS-142-1 alone. Coinhibition withl-NMMA and HS-142-1 significantly inhibited acetylcholine- and bradykinin-induced relaxation to a magnitude greater than either inhibitor alone. In summary, a novel interaction between the NO and the natriuretic peptide system is demonstrated by increased attenuation of endothelium-dependent relaxations to acetylcholine and bradykinin when both NO synthase and natriuretic peptide receptors are inhibited. These investigations support the concept of release of multiple endothelium-derived factors in response to acetylcholine- and bradykinin-receptor stimulation in endothelial cells, which may include CNP, as well as NO.

Role of Natriuretic Peptide Receptor Type C in Dahl Salt-Sensitive Hypertensive Rats

Hypertension ◽  
1997 ◽  
Vol 30 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Miki Nagase ◽  
Katsuyuki Ando ◽  
Takeshi Katafuchi ◽  
Akira Kato ◽  
Shigehisa Hirose ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Hypertensive Rats ◽  
Peptide Receptor ◽  
Type C
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