Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium

Molenaar, P.

doi:10.1016/0022-2828(92)93130-c

Cited by 25 publications

(32 citation statements)

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“…Activation of these receptors stimulates multiple intracellular signalling pathways and mediates diverse cellular effects (Ishikawa et al ., 1988a; 1988b; Moravec et al ., ). The relative abundance of ET receptors varies across the chambers and regions of the normal healthy heart, with the number of ET‐1 binding sites in atrial cells far exceeding those found in ventricular cells (Molenaar et al ., ). Functionally, the ET A and ET B receptors exhibit several key differences.…”

Section: Et Receptorsmentioning

confidence: 97%

“…Due to greater receptor abundance in the atria, the effects of ET‐1 are most well established in this chamber (Ishikawa et al ., ; Vigne et al ., ; Molenaar et al ., ). The atrial response to ET‐1 (e.g.…”

Section: Et‐1 In Cardiac Pacemaking and Contractilitymentioning

confidence: 97%

“…Moreover, the origin of the cardiac preparation studied is also a significant determinant of the response (Moravec et al ., ). This is not surprising given that the distribution and abundance of ET receptor isoforms varies across the chambers of the heart (Molenaar et al ., ; Russell and Davenport, ). Further diversity is provided by the experimental preparation – intact heart, chamber muscle strips or isolated cells.…”

Section: Et‐1 In Cardiac Pacemaking and Contractilitymentioning

confidence: 99%

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The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

Drawnel

Archer

Roderick

2012

British J Pharmacology

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Endothelin-1 (ET-1) is a critical autocrine and paracrine regulator of cardiac physiology and pathology. Produced locally within the myocardium in response to diverse mechanical and neurohormonal stimuli, ET-1 acutely modulates cardiac contractility. During pathological cardiovascular conditions such as ischaemia, left ventricular hypertrophy and heart failure, myocyte expression and activity of the entire ET-1 system is enhanced, allowing the peptide to both initiate and maintain maladaptive cellular responses. Both the acute and chronic effects of ET-1 are dependent on the activation of intracellular signalling pathways, regulated by the inositol-trisphosphate and diacylglycerol produced upon activation of the ETA receptor. Subsequent stimulation of protein kinases C and D, calmodulin-dependent kinase II, calcineurin and MAPKs modifies the systolic calcium transient, myofibril function and the activity of transcription factors that coordinate cellular remodelling. The precise nature of the cellular response to ET-1 is governed by the timing, localization and context of such signals, allowing the peptide to regulate both cardiomyocyte physiology and instigate disease. LINKED ARTICLESThis article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/ 10.1111/bph.2013.168.issue-2 AbbreviationsAngII, angiotensin II; CICR, calcium-induced-calcium release; Cn, calcineurin; ECC, excitation-contraction-coupling; IICR, IP3-induced calcium release; IP3R, inositol triphosphate receptor; MyBP-C, myosin binding protein C; RyR, ryanodine receptor; TnI, troponin I IntroductionEndothelin (ET)-1, ET-2 and ET-3 are a family of cyclic 21 amino acid peptides. The peptides are encoded within three separate yet highly conserved genes located on chromosomes 6, 1 and 20 in humans respectively (Inoue et al., 1989). ET-1 is the most well characterized member of this family. The peptide was initially isolated from the culture supernatant of porcine aortic endothelial cells and identified as a proteasesensitive vasoconstrictor. It remains the most potent vasoactive substance identified to date (Yanagisawa et al., 1988), performing an important function in the regulation of vascular smooth muscle tone. ET-1 also mediates effects on other cell types. Here, we discuss the role of ET-1 in the heart. We will focus on the actions of ET-1 on cardiac muscle and describe how the ET system contributes to cardiac regulation and autoregulation during health and disease. ET-1 in the heartThroughout life, ET-1 plays key roles in many aspects of cardiac physiology and pathology. It is involved in controlling aortic arch formation during development (Kurihara et al., 1995), is required for cardiomyocyte survival and prevents myocyte loss during ageing (Zhao et al., 2006). In the adult, ET-1 modulates coronary blood flow by regulation of vascular tone. Furthermore, by acting on its receptors expressed by atrial and ventricular myocytes, the peptide modulates cardiac muscle function directly (Hirata ...

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Section: Et Receptorsmentioning

confidence: 97%

Section: Et‐1 In Cardiac Pacemaking and Contractilitymentioning

confidence: 97%

Section: Et‐1 In Cardiac Pacemaking and Contractilitymentioning

confidence: 99%

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The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

Drawnel

Archer

Roderick

2012

British J Pharmacology

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“…Both ET A and ET B receptors are expressed in cardiomyocytes, with a dominance of ET A receptors (85–90%) (Molenaar et al . ). The ET A receptor is responsible for the positive inotropic effect of ET‐1 in rats (Takeuchi et al .…”

Section: Endothelin‐1 In the Regulation Of Cardiac Contractilitymentioning

confidence: 97%

Physiological regulation of cardiac contractility by endogenous reactive oxygen species

et al. 2012

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Increased production of reactive oxygen species (ROS) has been linked to the pathogenesis of congestive heart failure. However, emerging evidence suggests the involvement of ROS in the regulation of various physiological cellular processes in the myocardium. In this review, we summarize the latest findings regarding the role of ROS in the acute regulation of cardiac contractility. We discuss ROS-dependent modulation of the inotropic responses to G protein-coupled receptor agonists (e.g. β-adrenergic receptor agonists and endothelin-1), the potential cellular sources of ROS (e.g. NAD(P)H oxidases and mitochondria) and the proposed end-targets and signalling pathways by which ROS affect contractility. Accumulating new data supports the fundamental role of endogenously generated ROS to regulate cardiac function under physiological conditions.

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“…In contrast, stimulation of ET B receptors with the selective agonist, sarafotoxin (S6c), exerted an antiarrhythmic action on ischaemia‐induced arrhythmias in vivo ( Crockett et al ., 2000 ). Although ET B receptors are found within the heart predominantly in the conducting system and endocardium ( Molenaar et al ., 1993 ), no studies appear to have examined what electrophysiological effects they produce in whole hearts, if any such effects are more pronounced in the endo‐ vs the epicardium and if these could explain an antiarrhythmic action of ET B stimulation.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and haemodynamic effects of endothelin ET_A and ET_B receptors in normal and ischaemic working rabbit hearts

McCabe

Hicks

Kane

et al. 2005

British J Pharmacology

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1 The aims of this study were to determine if endothelin-1 (ET-1) under normal and ischaemic conditions exhibits a direct arrhythmogenic effect that is independent of its ability to cause coronary vasoconstriction, and to determine the contribution of the ET A and ET B receptor subtype. 2 ET A/B (with ET-1) and ET A (ET-1 in the presence of BQ-788) receptor activation resulted in a significant reduction in both epi-and endocardial monophasic action potential duration (MAPD 90 ). ET A receptor activation reduced both epi-and endocardial effective refractory period (ERP). This MAPD 90 and ERP shortening were associated with a reduction in coronary flow, myocardial contractility and induction of ventricular fibrillation (VF) during ERP measurement. 3 The ET B agonist sarafotoxin (S6c) had no marked, or concentration-dependent, effect on MAPD 90 , ERP, myocardial contractility or induction of arrhythmias. 4 Neither ET-1 nor S6c, given prior to coronary artery occlusion, significantly changed the ischaemia-induced dispersion of MAPD 90 , ERP or the % incidence of VF. 5 In conclusion, neither ET A nor ET B receptor stimulation has a direct arrhythmogenic effect in isolated rabbit hearts under normal or ischaemic conditions. The ET-1-induced arrhythmogenic effect observed in nonischaemic hearts is likely to be the result of the associated coronary vasoconstriction caused by ET A receptor stimulation resulting in myocardial ischaemia.

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Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium

Cited by 25 publications

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The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

Physiological regulation of cardiac contractility by endogenous reactive oxygen species

Electrophysiological and haemodynamic effects of endothelin ET_A and ET_B receptors in normal and ischaemic working rabbit hearts

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Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium

Cited by 25 publications

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The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

The role of the paracrine/autocrine mediator endothelin‐1 in regulation of cardiac contractility and growth

Physiological regulation of cardiac contractility by endogenous reactive oxygen species

Electrophysiological and haemodynamic effects of endothelin ETA and ETB receptors in normal and ischaemic working rabbit hearts

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Electrophysiological and haemodynamic effects of endothelin ET_A and ET_B receptors in normal and ischaemic working rabbit hearts