Ethanol Extract ofLepidium apetalumSeed Elicits Contractile Response and Attenuates Atrial Natriuretic Peptide Secretion in Beating Rabbit Atria

The seeds ofLepidium apetalumWilldenow (called “Tinglizi” in China and “Jungryukza” in Korea) have been used to discharge phlegm and improve dropsy in Oriental medicine. The present study investigated the effects of ethanol extract of the seeds ofLepidium apetalum(ELA) on atrial dynamics and atrial natriuretic peptide (ANP) secretion in beating rabbit atria. ELA increased atrial stroke volume, pulse pressure, and cAMP efflux, concomitantly attenuating ANP secretion in a dose-dependent manner. ELA-induced increases in atrial stroke volume, pulse pressure, and cAMP levels and decrease in ANP secretion were not inhibited by pretreatment with staurosporine, a nonspecific protein kinase inhibitor, or diltiazem and verapamil, the L-type Ca2+channel blockers, respectively. Helveticoside, a well-known digitalis-like cardiac glycosidic constituent of ELA, also increased atrial dynamics, including stroke volume and pulse pressure, without changing cAMP efflux and ANP secretion, and the effects of helveticoside were not inhibited by pretreatment with staurosporine, diltiazem, and verapamil. These results suggest that the ELA-induced positive inotropic activity in beating rabbit atria might, at least partly, be due to the digitalis-like activity of helveticoside rather than an increase in cAMP efflux.

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Distinct roles for L- and T-type Ca2+ channels in regulation of atrial ANP release

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.6.h2879 ◽

2000 ◽

Vol 279 (6) ◽

pp. H2879-H2888 ◽

Cited By ~ 18

Author(s):

Jin Fu Wen ◽

Xun Cui ◽

Jin Sub Ahn ◽

Suhn Hee Kim ◽

Kyung Hwan Seul ◽

...

Keyword(s):

Stroke Volume ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Pulse Pressure ◽

Extracellular Fluid ◽

Intracellular Ca ◽

Continuous Presence ◽

The Relationship ◽

Rabbit Atria ◽

Ca2 Channels

Atrial secretion of atrial natriuretic peptide (ANP) has been shown to be regulated by atrial workload. Although modulating factors for the secretion of ANP have been reported, the role for intracellular Ca2+ on the secretion of ANP has been controversial. The purpose of the present study was to define roles for L- and T-type Ca2+ channels in the regulation of ANP secretion in perfused beating rabbit atria. BAY K 8644 (BAY K) increased atrial stroke volume and pulse pressure. BAY K suppressed ANP secretion and ANP concentration in terms of extracellular fluid (ECF) translocation concomitantly with an increase in atrial dynamics. BAY K shifted the relationship between ANP secretion and ECF translocation downward and rightward. These results indicate that BAY K inhibits myocytic release of ANP. In the continuous presence of BAY K, diltiazem reversed the effects of BAY K. Diltiazem alone increased ANP secretion and ANP concentration along with a decrease in atrial dynamics. Diltiazem shifted relationships between ANP secretion and atrial stroke volume or ECF translocation leftward. The T-type Ca2+ channel inhibitor mibefradil decreased atrial dynamics. Mibefradil inhibited ANP secretion and ANP concentration in contrast with the L-type Ca2+ channel inhibitor. These results suggest that activation of L- and T-type Ca2+ channels elicits opposite effects on atrial myocytic release of ANP.

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Atrial Natriuretic Peptide Improves Neurite Outgrowth from Spiral Ganglion Neurons In Vitro through a cGMP-Dependent Manner

Neural Plasticity ◽

10.1155/2020/8831735 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Jie Wang ◽

Jian-hua Qiu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Critical Role ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Dependent Manner ◽

Ganglion Neurons ◽

Atrial Natriuretic

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the spiral ganglion (SG), while their degeneration or loss would cause sensorineural hearing loss. As a cardiac-derived hormone, atrial natriuretic peptide (ANP) plays a critical role in cardiovascular homeostasis through binding to its functional receptors (NPR-A and NPR-C). ANP and its receptors are widely expressed in the mammalian nervous system where they could be implicated in the regulation of multiple neural functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors in the inner ear, their presence within the cochlear SG and their regulatory roles during auditory neurotransmission and development remain largely unknown. Based on our previous findings, we investigated the expression patterns of ANP and its receptors in the cochlear SG and dissociated SGNs and determined the influence of ANP on neurite outgrowth in vitro by using organotypic SG explants and dissociated SGN cultures from postnatal rats. We have demonstrated that ANP and its receptors are expressed in neurons within the cochlear SG of postnatal rat, while ANP may promote neurite outgrowth of SGNs via the NPR-A/cGMP/PKG pathway in a dose-dependent manner. These results indicate that ANP would play a role in normal neuritogenesis of SGN during cochlear development and represents a potential therapeutic candidate to enhance regeneration and regrowth of SGN neurites.

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Atrial natriuretic peptide in the eel, Anguilla anguilla L.: its cardiac distribution, receptors and actions on isolated branchial cells

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0090103 ◽

1992 ◽

Vol 9 (2) ◽

pp. 103-114 ◽

Cited By ~ 14

Author(s):

C. L. Broadhead ◽

U. T. O'Sullivan ◽

C. F. Deacon ◽

I. W. Henderson

Keyword(s):

Sodium Chloride ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Binding Sites ◽

Specific Binding ◽

Anguilla Anguilla ◽

Chloride Cells ◽

Dependent Manner ◽

Single Class ◽

Atrial Natriuretic

ABSTRACT The presence of atrial natriuretic peptide (ANP) and the nature of its binding sites were studied in freshwater (FW)- and seawater (SW)-adapted eels using a heterologous analogue, that of the rat (rANP). Rat ANP-like immunoreactivity was demonstrated in the cardiac atria and ventricles of both FW and SW eels, and electron-dense ANP-like granules were observed. The atria and ventricles of FW eels contained significantly more granules than those of SW animals and, in both types, the atria were more granular than the ventricles. Specific binding sites for rANP were demonstrated by displacement and uptake experiments using labelled rANP in dispersed eel branchial cell preparations, enriched in chloride cells. The concentration of rANP required to produce a 50% inhibition of binding in FW cells was significantly lower than that in SW cells. Scatchard analyses revealed the presence of two classes of binding site in SW eel branchial cells but only a single class of receptor in FW cells. The affinity of the FW receptor was not significantly different from that of the SW high affinity site. Rat ANP stimulated the production of cyclic GMP (cGMP) in a dose-dependent manner, and both basal and stimulated levels of cGMP were significantly greater in SW branchial cells. These studies suggest that ANP is involved in the adaptation of the euryhaline eel to differing environmental salinities; the levels of the peptide in the heart alter with changing salinity, and the nature of the receptors in the sodium chloride-transporting epithelium of the gill changes in response to the need either to eliminate or to absorb sodium chloride.

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The protein tyrosine kinase inhibitor genistein suppresses hypoxia-induced atrial natriuretic peptide secretion mediated by the PI3K/Akt-HIF-1α pathway in isolated beating rat atria

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0503 ◽

2021 ◽

pp. 1-7

Author(s):

Qiu-li Zhang ◽

Ping Li ◽

Lan Hong ◽

Rui-zhuang Li ◽

Jia-qi Wang ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Tyrosine Kinase ◽

Natriuretic Peptide ◽

Protein Tyrosine Kinase ◽

Kinase Inhibitor ◽

Acute Hypoxia ◽

Hypoxia Inducible Factor ◽

Protein Tyrosine ◽

Downstream Signaling ◽

Atrial Natriuretic

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1α (HIF-1α), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 μM). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 μM) or CAY10585 (10 μM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 μM) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1α. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1α dependent pathway.

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Endogenous atrial natriuretic peptide inhibits endothelin-1 secretion in dogs with severe congestive heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.5.h1819 ◽

1996 ◽

Vol 270 (5) ◽

pp. H1819-H1824 ◽

Cited By ~ 8

Author(s):

A. Wada ◽

T. Tsutamato ◽

Y. Maeda ◽

T. Kanamori ◽

Y. Matsuda ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Arterial Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Severe Congestive Heart Failure ◽

Dependent Manner ◽

Endothelin 1 ◽

Atrial Natriuretic

Atrial natriuretic peptide (ANP) has been shown to counteract the response of endothelin-1 (ET-1), but whether endogenous ANP actually inhibits the systemic release of ET-1 in vivo has not yet been determined. We administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled ANP receptor, to conscious dogs with severe congestive heart failure (CHF) produced by rapid right ventricular pacing (n = 5, for 22 days) at doses of 0.3, 1.0, and 3.0 mg/kg at 30-minutes intervals. In the present study, plasma ANP and ET-1 levels were significantly elevated in CHF(348 +/-58 and 4.54 +/- 0.60 pg/ml, respectively compared with those in control dogs (65 +/- 4, P < 0.01, 1.30 +/- 0.17 pg/ml, P < 0.001). HS inhibited plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a biological market of endogenous ANP activity, in a dose-dependent manner from 21.8 +/- 2.2 to 7.2 +/- 1.4 pmol/ml (P < 0.001), with concomitant significant increases in plasma ET-1 levels from 4.54 +/- 0.60 to 6.60 +/- 0.72 pg/ml (P < 0.05). There was a significant negative correlation between the decrease in plasma cGMP and the increment in plasma ET-1 (r = -0.64, P < 0.01). Despite these responses, mean arterial pressure and pulmonary arterial pressure did not change significantly. Plasma angiotensin II and arginine vasopressin levels, both of which have been reported to stimulate ET-1 secretion in vitro, also showed no significant changes. These results strongly suggest that endogenous ANP directly inhibits endogenous ET-1 secretion through a cGMP-mediated pathway in chronic severe CHF.

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Ouabain stimulates atrial natriuretic peptide secretion via the endothelin-1/ETB receptor-mediated pathway in beating rabbit atria

Life Sciences ◽

10.1016/j.lfs.2012.04.008 ◽

2012 ◽

Vol 90 (19-20) ◽

pp. 793-798 ◽

Cited By ~ 12

Author(s):

Li-ping Liu ◽

Lan Hong ◽

Li Yu ◽

Hai-yan Li ◽

Da-zhi Ding ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Endothelin 1 ◽

Etb Receptor ◽

Peptide Secretion ◽

Rabbit Atria ◽

Atrial Natriuretic

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MAPK and PI3K pathways regulate hypoxia-induced atrial natriuretic peptide secretion by controlling HIF-1 alpha expression in beating rabbit atria

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.07.106 ◽

2013 ◽

Vol 438 (3) ◽

pp. 507-512 ◽

Cited By ~ 20

Author(s):

Qiu-li Zhang ◽

Bai-ri Cui ◽

Hai-yan Li ◽

Ping Li ◽

Lan Hong ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Peptide Secretion ◽

Rabbit Atria ◽

Atrial Natriuretic

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Prolonged Atrial Natriuretic Peptide Exposure Stimulates Guanylyl Cyclase-A Degradation

Endocrinology ◽

10.1210/en.2009-1239 ◽

2010 ◽

Vol 151 (6) ◽

pp. 2769-2776 ◽

Cited By ~ 15

Author(s):

Darcy R. Flora ◽

Lincoln R. Potter

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Guanylyl Cyclase ◽

Cultured Cells ◽

Volume Overload ◽

Receptor Expression ◽

Dependent Manner ◽

Down Regulation ◽

Time Required ◽

Atrial Natriuretic

Natriuretic peptide receptor-A (NPR-A), also known as guanylyl cyclase-A, is a transmembrane receptor guanylyl cyclase that is activated by the cardiac hormones atrial natriuretic peptide and B-type natriuretic peptide. Although ligand-dependent NPR-A degradation (also known as down-regulation) is widely acknowledged in human and animal models of volume overload, down-regulation in cultured cells is controversial. Here, we examined the effect of ANP exposure on cellular NPR-A levels as a function of time. Relative receptor concentrations were estimated using guanylyl cyclase and immunoblot assays in a wide variety of cell lines that endogenously or exogenously expressed low or high numbers of receptors. ANP exposures of 1 h markedly reduced hormone-dependent but not detergent-dependent guanylyl cyclase activities in membranes from exposed cells. However, 1-h ANP exposures did not significantly reduce NPR-A concentrations in any cell line. In contrast, exposures of greater than 1 h reduced receptor concentrations in a time-dependent manner. The time required for half of the receptors to be degraded (t1/2) in primary bovine aortic endothelial and immortalized HeLa cells was approximately 8 h. In contrast, a 24-h exposure of ANP to 293T cells stably overexpressing NPR-A caused less than half of the receptors to be degraded. To our knowledge, this is the first report to directly measure NPR-A down-regulation in endogenously expressing cells. We conclude that down-regulation is a universal property of NPR-A but is relatively slow and varies with receptor expression levels and cell type.

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