scholarly journals Activation of TGF‐β mediated SMAD pathway induces cardiac fibrosis in mice carrying targeted disruption of guanylyl cyclase/natriuretic peptide receptor‐A gene (547.17)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Umadevi Subramanian ◽  
Venkateswara Gogulamudi ◽  
David Chen ◽  
Kailash Pandey
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Cardiac Fibrosis ◽  
Natriuretic Peptide Receptor ◽  
Targeted Disruption ◽  
Smad Pathway ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A

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.

Targeted disruption of the gene for natriuretic peptide receptor-A worsens hypoxia-induced cardiac hypertrophy

2002 ◽  
Vol 282 (1) ◽  
pp. H58-H65 ◽  
Author(s):  
James R. Klinger ◽  
Rod R. Warburton ◽  
Linda Pietras ◽  
Paula Oliver ◽  
Jennifer Fox ◽  
...  
Keyword(s):  
Body Weight ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Left Ventricular ◽  
Natriuretic Peptide Receptor ◽  
Targeted Disruption ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A

Targeted disruption of the gene for natriuretic peptide receptor-A (NPR-A) worsens pulmonary hypertension and right ventricular hypertrophy during hypoxia, but its effect on left ventricular mass and systemic pressures is not known. We examined the effect of 3 wk of hypobaric hypoxia (0.5 atm) on right and left ventricular pressure and mass in mice with 2 (wild type), 1, or 0 copies of Npr1, the gene that encodes for NPR-A in mice. Under normoxic conditions, right ventricular peak pressure (RVPP) was greater in 0 than in 2 copy mice, but there were no genotype-related differences in carotid artery PP (CAPP). The left ventricular free wall weight-to-body weight (LV/body wt) ratio was greater in 0 than in 2 copy mice and there was a trend toward a greater right ventricular weight-to-body weight (RV/body wt) ratio. Three weeks of hypoxia increased RVPP and RV/body wt in all genotypes. The increase in RVPP was similar in all genotypes (11–14 mmHg), but the hypoxia-induced increase in RV/body wt was more than twice as great in 0 copy mice than in 2 copy mice (1.11 ± 0.06 to 2.65 ± 0.46 vs. 0.96 ± 0.04 to 1.4 ± 0.09, P < 0.05). Chronic hypoxia had no effect on CAPP in any genotype and did not effect LV/body wt in 1 or 2 copy mice, but increased LV/body wt 41% in 0 copy mice. We conclude that absent expression of NPR-A worsens right ventricular hypertrophy and causes left ventricular hypertrophy during exposure to chronic hypoxia without increasing pulmonary or systemic arterial pressure responses.

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