Atrial natriuretic peptide decreases contractility of cultured chick ventricular cells

doi:10.1016/0024-3205(89)90433-5

Life Sciences

Volume 45, Issue 1, 1989, Pages 41-48

https://doi.org/10.1016/0024-3205(89)90433-5 Get rights and content

Abstract

To determine whether atrial natriuretic peptide (ANP) has an inotropic effet, the contractility of spontaneously beating cultured chick embryo ventricular cells was studied in response to rat-ANP (1–23) superfused at concentrations ranging from 10⁻¹⁰ M to 2.5 × 10⁻⁷ M. r-ANP reversibly decreased contractility with a threshold concentration of 10⁻⁸ M; at the highest concentration, r-ANP decreased contractility to a moderate extent (−30 ± 4 %) r-ANP increased dose-dependently intracellular cGMP levels. Stimulation of contractility with [Ca2+], the calcium-channel agonist BAY K 8644 or isoproterenol attenuated to various degrees the inhibitory effect of r-ANP. By contrast, the inhibitory effect of r-ANP on contractility was unchanged or even enhanced after stimulation of contractility by angiotensin II. There was no difference in r-ANP-induced increase in cGMP whether cells were pre-incubated with angiotensin II or not. These results indicate that r-ANP was able to decrease contractility of cultured cardiac myocytes and suggest a preferential antagonism of the inotropic effect of angiontensin II.

References (22)

M.B. Anand-Srivastava et al.
Biochem. Biophys. Res. Commun.
(1984)
J. Bergey et al.
Eur. J. Pharmacol.
(1985)
Y. Hirata et al.
Eur. J. Pharmacol.
(1987)
E. Leung et al.
Life Sci.
(1986)
W.H. Barry et al.
J. Physiol. (London)
(1982)
G.E. Bilder et al.
Y.W. Chien et al.
Am. J. Physiol.
(1987)
L. Criscione et al.
J. Cardiovasc. Pharmacol.
(1987)
A.J. de Bold et al.
Can. J. Physiol. Pharmacol.
(1983)
A. Dosemeci et al.
Circ. Res.
(1988)

R. Fischmeister et al.

J. Phys.

(1987)

Cited by (21)

Chapter 3 Natriuretic Peptides in Vascular Physiology and Pathology
2008, International Review of Cell and Molecular Biology
Citation Excerpt :
ANP and BNP have been reported to show either negative or no effects on cardiac contractility when administered exogenously and even in the same species the findings are conflicting. ANP has been shown to have no effect in isolated rat cardiomyocytes or in isolated rat, feline or canine heart (Burnett et al., 1987; Hirose et al., 1998; MacDonell and Diamond, 1997; Yanagisawa et al., 1987); however, ANP exerts a negative inotropic effect on avian cardiomyocytes or rat ventricular trabeculae (Stone et al., 1990; Vaxelaire et al., 1989). The inotropic effects of CNP are not less inconsistent and contradictory, and both positive and negative effects have been reported (D'Souza et al., 2004).
Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C‐type natriuretic peptide (CNP), and Dendroaspis‐type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti‐ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR‐A), type B natriuretic peptide receptor (NPR‐B), and type C natriuretic peptide receptor (NPR‐C). NPR‐A and NPR‐B are guanylyl cyclase receptors that increase intracellular cGMP concentration and activate cGMP‐dependent protein kinases. NPR‐C has been presented as a clearance receptor and its activation also results in inhibition of adenylyl cyclase activity. The wide range of effects of natriuretic peptides might be the base for the development of new therapeutic strategies of great benefit in patients with cardiovascular problems including coronary artery disease or heart failure. This review summarizes current literature concerning natriuretic peptides, their receptors and their effects on fluid/electrolyte balance, and vascular and cardiac physiology and pathology, including primary hypertension and myocardial infarction. In addition, we will attempt to provide an update on important issues regarding natriuretic peptides in congestive heart failure.
Autocrine and paracrine actions of natriuretic peptides in the heart
2004, Pharmacology and Therapeutics
The natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are a family of polypeptide mediators exerting numerous actions in cardiovascular homeostasis. ANP and BNP are cardiac derived, being secreted and up-regulated in myocardium in response to many pathophysiological stimuli. CNP is an endothelium-derived mediator. The classical endocrine effects of ANP and BNP on fluid homeostasis and blood pressure, especially in conditions characterised by left ventricular dysfunction, are well recognised and extensively researched. However, there is accumulating evidence that, in addition to endocrine actions, ANP and BNP exhibit important autocrine and paracrine functions within the heart and coronary circulation. These include regulation of myocyte growth, inhibition of fibroblast proliferation and extracellular matrix deposition, a cytoprotective anti-ischaemic (preconditioning-like) function, and influences on coronary endothelium and vascular smooth muscle proliferation and contractility. Most if not all of these actions can be ascribed to particulate guanylyl cyclase activation because the ANP/BNP receptor, natriuretic peptide receptor (NPR)-A, has an intracellular guanylyl cyclase domain. Subsequent elevation of the intracellular second messenger cGMP may exert diverse physiological effects through activation of cGMP-dependent protein kinases (cGK), predominantly cGK-I. However, there appear to be other contributory mechanisms in several of these actions, including the augmentation of nitric oxide synthesis. These diverse actions may represent counterregulatory mechanisms in the pathophysiology of many cardiovascular diseases, not just those typified by left ventricular dysfunction. Ultimately, insights from the autocrine/paracrine actions of natriuretic peptides may provide routes to therapeutic application in cardiac diseases of natriuretic peptides and drugs that modify their availability.
Cardiac role of frog ANF: Negative inotropism and binding sites in Rana esculenta
2003, Regulatory Peptides
To elucidate the role of atrial natriuretic peptides (NPs) in the amphibian heart, the myotropic effects and the cardiac distribution of frog atrial natriuretic factor (fANF) have been studied in Rana esculenta. Spontaneously, beating in vitro isolated working heart preparations were treated with increased concentrations (10⁻¹¹–10⁻⁸ M) of fANF-(1–24). The peptide at 10⁻⁹ and 10⁻⁸ M significantly reduced heart rate (HR) and, on the electrically paced preparations, decreased cardiac output (CO), stroke volume (SV) and work. Such negative inotropism was abolished by pretreatment with the pertussis toxin or by blocking the particulate guanylate cyclase (GC) with anantin while it was independent both from the functional impairment of the endocardium–endothelium by Triton X-100 and the inhibition of the soluble guanylate cyclase by 1 H-(1,2,4,) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ). By autoradiography, two classes of high and low affinity NPs binding sites were detected in the ventricular endocardium and myocardium and in the bulbus arteriosus. The analysis of displacement binding data using the radioligand [¹²⁵I]-rat atrial natriuretic peptide [¹²⁵I-rANP-(1–28)], its cold counterpart and the fANF-(1–24) showed that in the ventricular myocardium, the low affinity NPs sites bound both the heterologous and the homologous ligands at a concentration close to that responsible for the negative inotropism and chronotropism.
Endothelin-1, endothelin-1 receptors and cardiac natriuretic peptides in failing human heart
2001, Life Sciences
Endothelin (ET)-1 is a potent vasoconstrictor peptide produced in the myocardium that can exert important effects on cardiac myocyte growth and phenotype; cardiac natriuretic peptides (ANP and BNP) are known to act as physiological antagonists of ET-1. In this study a comparative determination of ET-1 receptors and of the local productions of ET-1 and of ANP and BNP was made in different sites of failing and nonfailing hearts. Tissue from right and left atrium, right and left ventricle and interventricular septum from seven adult heart transplant recipients with end-stage idiopathic dilated cardiomyopathy (functional class III and IV, with ejection fraction < 35%) and from four post-mortem subjects without cardiac complications was analyzed. In failing hearts we observed a tendency to increase of density of binding sites, most evident in left ventricle (62.6 ± 22.6 fmol/mg protein vs. 29.0 ± 3.3, mean ± SEM, p = ns). A prevalence of ET-A subclass, observed in all samples, resulted more pronounced in failing hearts where this increase, found in all the cardiac regions, was more evident in left ventricle (p = 0.0007 vs nonfailing hearts). The local concentrations of ET-1, ANP and BNP resulted significantly increased in failing hearts with respect to controls in all sides of the heart. In failing hearts we have observed a tendency to increase in endothelin receptor density mainly due to a significant upregulation of ET-A subtype and a parallel increase of the tissue levels of ANP, BNP and ET-1 indicating an activation of these systems in heart failure.
Effects of exogenous and endogenous nitric oxide on the contractile function of cultured chick embryo ventricular myocytes
1997, Journal of Molecular and Cellular Cardiology
Nitric oxide (NO) has been shown to be a ubiquitous intercellular autacoid in the heart and, in cultured rat ventricular myocytes, to decrease the contractile responsiveness to isoproterenol (ISO). The aim of the present study was to investigate whether exogenous (sodium nitroprusside, SNP) or endogenous nitric oxide generated froml-arginine modulated the response to ISO in cultured chick embryo ventricular myocytes. SNP 1μmorl-arginine 1 mmhad no effect on baseline contractile function. Superfusion with ISO 100 nmsignificantly increased myocyte amplitude of shortening to 1.31±0.06 (ratio to baseline amplitude). Initial superfusion with SNP 1μmorl-arginine 1 mmattenuated the response to ISO to 0.89±0.05 and 1.09±0.07 respectively (P<0.05). Potassium ferrocyanide which is not a NO donor andd-arginine the inactive substrate of NO synthase did not attenuate the response to ISO. Myocyte cGMP content was significantly increased by incubation with SNP 1μm(31.65±3 fmol/well) but not byl-arginine 1 mm(11.1±0.3 fmol/well) as compared to myocytes incubated in control medium (11±0.9 fmol/well). Preincubation with SNP 1μmorl-arginine 1 mmsignificantly attenuated the ISO mediated-increase in cAMP content from 4.33±0.2 pmol/well (ISO 100 nmalone) to 1.48±0.36 fmol/well and 1.72±0.21 pmol/well respectively. Potassium ferrocyanide andd-arginine had no effect on myocyte cGMP or cAMP content. Chick embryo myocytes have measurable andlNMMA-inhibited NO synthase activity as measured by the conversion of [³H]l-arginine to [³H]l-citrulline. In conclusion, these results demonstrate that in cultured chick embryo ventricular myocytes both exogenous and endogenous NO elevate cGMP. This may account for the inhibition ofβ-adrenergic agonist-stimulated increases in cAMP and amplitude of shortening via an unidentified intracellular negative coupling.
Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility
1996, European Journal of Pharmacology
We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10⁻⁸ M) increased chick cardiomyocyte contractility by 20–25% between 5 and 15 min (P < 0.05). Although ChNP (3 × 10⁻⁷ M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

View all citing articles on Scopus

View full text

Atrial natriuretic peptide decreases contractility of cultured chick ventricular cells

Abstract

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Life Sci.

J. Physiol. (London)

Am. J. Physiol.

J. Cardiovasc. Pharmacol.

Can. J. Physiol. Pharmacol.

Circ. Res.

J. Phys.