Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes

1991 ◽  
Vol 261 (2) ◽  
pp. E177-E182 ◽  
Author(s):  
D. G. Gardner ◽  
E. D. Newman ◽  
K. K. Nakamura ◽  
K. P. Nguyen
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Primary Cultures ◽  
Secretory Activity ◽  
Neonatal Rat ◽  
Regulatory Function ◽  
Mrna Accumulation ◽  
Calmodulin Antagonist ◽  
Natriuretic Hormone ◽  
Atrial Natriuretic

Endothelin (ET) effected a dose-dependent increment in atrial natriuretic peptide (ANP) secretion and ANP mRNA accumulation in neonatal rat atrial and ventricular cardiocytes but had no effect on the processing of the ANP prohormone to the mature ANP product. The secretagogue effect was not limited by cell density. Both basal and ET-dependent secretory activity were abrogated by the calmodulin antagonist calmidazolium but were unaffected by meclophenamate or pertussis toxin. The magnitude of the ET-dependent increment in ANP secretion was amplified by culturing the cells in a dynamically pulsating (vs. static) environment, implying an interaction between mechanical and agonist-mediated secretory stimuli in this system. ET also promoted immunoreactive ANP release from primary cultures of fetal rat hypothalamic cultures, suggesting that this regulatory function may be generally employed in ANP gene-expressing cells. These findings demonstrate that ET has parallel effects on ANP synthesis and secretion and support a role for this peptide in the regulation of local and circulating levels of the natriuretic hormone.

Natriuretic Hormone: A Contribution to the Development of a Hypothesis

Physiology ◽  
1991 ◽  
Vol 6 (3) ◽  
pp. 114-118
Author(s):  
B Lichardus
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Hormone ◽  
Endogenous Ouabain ◽  
Experimental Background ◽  
Atrial Natriuretic

For two decades before the discovery of atrial natriuretic peptide and the recent announcement of the isolation of endogenous ouabain, the experimental background for the hypothesis of the existence of a natriuretic hormone, mostly furnished by a few laboratories, kept this challenge alive.

scholarly journals Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

1992 ◽  
Vol 12 (1) ◽  
pp. 292-301 ◽  
Author(s):  
B Kovacic-Milivojević ◽  
D G Gardner
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Transcriptional Activation ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Neonatal Rat ◽  
Regulatory Sequence ◽  
Mobility Shift ◽  
Human Atrial Natriuretic Peptide ◽  
Atrial Natriuretic

Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression.

PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways

2014 ◽  
Vol 306 (8) ◽  
pp. H1246-H1252 ◽  
Author(s):  
C. Vettel ◽  
S. Lämmle ◽  
S. Ewens ◽  
C. Cervirgen ◽  
J. Emons ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sodium Nitroprusside ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Nitric Oxide Donor ◽  
Signal Molecules ◽  
Protective Mechanism ◽  
Camp Hydrolysis ◽  
Camp And Cgmp ◽  
Atrial Natriuretic

Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide- and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure.

Atrial natriuretic peptide gene expression and its secretion by pneumocytes derived from neonatal rat lungs

1988 ◽  
Vol 156 (2) ◽  
pp. 619-627 ◽  
Author(s):  
Hiroaki Matsubara ◽  
Yasukiyo Mori ◽  
Yukihisa Umeda ◽  
Shinzo Oikawa ◽  
Hiroshi Nakazato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Rat Lungs ◽  
Peptide Gene ◽  
Atrial Natriuretic

Atrial natriuretic peptide: Evidence of action as a natriuretic hormone at physiological plasma concentrations in man

1987 ◽  
Vol 72 (3) ◽  
pp. 305-312 ◽  
Author(s):  
J. V. Anderson ◽  
J. Donckier ◽  
N. N. Payne ◽  
J. Beacham ◽  
J. D. H. Slater ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Natriuretic Hormone ◽  
Plasma Aldosterone Concentration ◽  
Water Excretion ◽  
Physiological Range ◽  
Atrial Natriuretic

1. The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli. 2. We infused human α-ANP (1–28) at a calculated rate of 1.2 pmol min−1 kg−1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 ± 1.5 to 20.9 ± 1.9 pmol/l. 3. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 ± 18 to 182 ± 30 μmol/min (P < 0.001) and a 28% increase of mean water excretion from 10.8 ± 0.8 to 13.8 ± 1.6 ml/min (P < 0.01). 4. The infusion suppressed mean plasma renin activity from 1.55 ± 0.10 to 1.17 ± 0.06 pmol of ANG I h−1 ml−1 (P < 0.001). Mean plasma aldosterone concentration (242 ± 16 basally and 215 ± 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study. 5. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day. 6. The demonstration that recreation of plasma concentrations of ANP within the physiological range by intravenous infusion induces a natriuresis provides new evidence supporting the role of ANP as a natriuretic hormone.

Production and Differential Endocrine Regulation of Atrial Natriuretic Peptide in Neuron-Enriched Primary Cultures*

Endocrinology ◽  
1991 ◽  
Vol 128 (1) ◽  
pp. 5-12 ◽  
Author(s):  
C. F. DESCHEPPER ◽  
K. P. T. NGUYEN ◽  
M. C. LAPOINTE ◽  
K. R. ZAHS ◽  
D. G. GARDNER
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Primary Cultures ◽  
Endocrine Regulation ◽  
Atrial Natriuretic
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