Negative Chronotropic Effect of Endothelin 1 Mediated Through ET
            <sub>A</sub>
            Receptors in Guinea Pig Atria

Ono, Koji; Eto, Koji; Sakamoto, Aiji; Masaki, Τοmoh; Shibata, Katsushi; Sada, Toshio; Hashimoto, Keitaro; Tsujimoto, Gozoh

doi:10.1161/01.res.76.2.284

Cited by 38 publications

(41 citation statements)

References 41 publications

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“…The results of the present study are consistent with this hypothesis, inasmuch as ET-1 caused an increase in the open-state probability of I CaL in rat cardiac myocytes. However, previous investigations examining the effect of ET-1 on I CaL have produced conflicting results, with decreases (Lauer et al, 1992;Boixel et al, 2001), increases (Cheng et al, 1995;Ono et al, 1995), Fig. 4.…”

Section: Discussionmentioning

confidence: 95%

“…However, the effect of ET-1 on I CaL still remains unclear. For example, some studies of ET-1 have shown clear increases in I CaL (Lauer et al, 1992;Boixel et al, 2001), whereas others have shown a decrease in I CaL (Cheng et al, 1995;Ono et al, 1995) or no effect (Tohse et al, 1990). These contradictory data may be due to the wide differences in experimental conditions, including different species, tissues, and preparations.…”

mentioning

confidence: 98%

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Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Zeng

Zhou²,

Yao³

et al. 2008

J Pharmacol Exp Ther

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It has been shown that reactive oxygen species (ROS) are involved in the intracellular signaling response to G-protein coupled receptor stimuli in vascular smooth muscle cells and in neurons. In the present study, we tested the hypothesis that NAD(P)H oxidasederived ROS are involved endothelin-1 (ET-1)-induced L-type calcium channel activation in isolated cardiac myocytes. ET-1 (10 nM) induced a 2-fold increase in L-type calcium channel openstate probability (NPo). This effect of ET-1 was abolished by. Pretreatment of cells with the ROS scavenger tempol (100 M), polyethylene glycol-superoxide dismutase (SOD, 25 U/ml), or the NAD(P)H-oxidase inhibitor gp91ds-tat ([H]RKKRRQRRR-CSTRIR-RQL[NH 3 ]) (5 M) significantly attenuated ET-1-induced increases in calcium channel NPo. Tempol, SOD, and gp91ds-tat alone had no effect on basal calcium channel activity. In addition, ET-1 significantly increased NAD(P)H oxidase activity and elevated intracellular superoxide levels in cultured cardiac myocytes. The superoxide generator, xanthine-xanthine oxidase (10 mM, 20 mU/ ml), also increased calcium channel NPo in cardiac myocytes, mimicking the effect of ET-1. These observations provide the first evidence that ET-1 induces the activation of L-type Ca 2ϩ channels via stimulation of NAD(P)H-derived superoxide production in cardiac myocytes.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 98%

Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Zeng

Zhou²,

Yao³

et al. 2008

J Pharmacol Exp Ther

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“…Thus, ET-1 administration decreased the L-type Ca 2+ current in isolated canine ventricular myocytes [86,87], in guinea pig [88], rabbit [89] and human myocytes [90]. In guinea pig ventricular myocytes, ET-1 had little effect on basal L-type Ca 2+ current but it did reduce this current enhanced by β 1 adrenoceptor stimulation [91].…”

Section: Mechanisms Underlying the Pro-arrhythmic Effect Of Et-1mentioning

confidence: 99%

Endothelin and the Ischaemic Heart

Wainwright

McCabe²,

Kane³

2005

CVP

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IntroductionIt has been widely documented that plasma ET-1 and big ET-1 levels are increased in patients within a day of onset of acute myocardial infarction [1,2,3,4]. Similar changes in systemic plasma ET-1 are seen in animal models of myocardial ischaemia [5,6]. The source of the released ET-1 appears to be the area subjected to ischaemic damage, since in a study in anaesthetised pigs both short and long periods of left anterior descending (LAD) coronary artery occlusion were found to enhance overflow of ET-1 from the area of myocardium subjected to the ischaemia/reperfusion insult [7]. The myocardial tissue level of ET-1 has been found to be increased by 3 to 7 fold in the ischaemic area compared to the non-ischaemic myocardium, suggesting an increased biosynthesis of ET-1 during ischaemia/reperfusion [5,7]. Indeed, the demonstration of increased ET-1 mRNA levels in cardiomyocytes subjected to ischaemia [8], supports this notion that that the raised circulating levels of endothelin are not simply due to release of stored peptide. The observation that ischaemia and reperfusion increases 125 I-labelled ET-1 binding sites in rat cardiac membranes [9] further supports the view that the endothelin system is up-regulated during these events, although the observation that there is no difference in ET-1 mRNA levels between animals subjected to ischaemia only and hearts subjected to ischaemia followed by reperfusion, implies that it is ischaemia that stimulates enhanced ET-1 production. Taken together, these observations have led to the concept that endothelin may play an important role in determining the outcome of myocardial ischaemia/reperfusion. Based on our knowledge that ET-1 is a potent vasoconstrictor peptide, early hypotheses focused on the role of ET-1 as a detrimental factor in the 3 ischaemic/reperfused heart. However, over the last decade or so, as our understanding of the cellular effects of endothelin has extended beyond that of vasoconstriction, evidence is emerging that endothelin may play a very complex role in the setting of the ischaemic heart, with the potential to both contribute to cellular injury and cellular repair. The aim of this review therefore is to provide an overview of the effects of endothelin on the cardiomyocyte, in the setting of myocardial ischaemia, and within this to consider not only its actions mediated through vasoconstriction, but also through its effects on ion channels, cellular integrity and inflammatory cells. Contribution of endothelin to ischaemia/reperfusion-induced myocardial injury.The possibility that the coronary vasoconstrictor effects of endothelin could play a role in the development of injury resulting from myocardial ischaemia arose following a number of demonstrations that intracoronary infusion of exogenous ET-1 reduces coronary blood flow by approximately 90% [10][11][12], resulting in marked myocardial ischaemia. Substantive evidence for a contributory role of endogenous ET-1 in infarct extension subsequently emanated from studies that demonstrated that ...

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“…Electrophysiological studies with voltage-clamped isolated cardiomyocytes suggest that ET has cardioprotective, "membrane stabilizing" properties; it inhibits the protein kinase A-dependent chloride current (244,425,426) whose conductance is induced by catecholamines through ␤-adrenergic receptors. By shortening the action potential duration, it thereby counteracts the simultaneously increased L-type Ca 2ϩ current.…”

Section: Cardiac Endothelium and Rhythmicity Of The Heartmentioning

confidence: 99%

Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity

Brutsaert

2003

Physiological Reviews

595

533

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Experimental work during the past 15 years has demonstrated that endothelial cells in the heart play an obligatory role in regulating and maintaining cardiac function, in particular, at the endocardium and in the myocardial capillaries where endothelial cells directly interact with adjacent cardiomyocytes. The emerging field of targeted gene manipulation has led to the contention that cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal cardiac development and growth. Some of the molecular mechanisms and cellular signals governing this interaction, such as neuregulin, vascular endothelial growth factor, and angiopoietin, continue to maintain phenotype and survival of cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular endothelial cells, also express and release a variety of auto- and paracrine agents, such as nitric oxide, endothelin, prostaglandin I2, and angiotensin II, which directly influence cardiac metabolism, growth, contractile performance, and rhythmicity of the adult heart. The synthesis, secretion, and, most importantly, the activities of these endothelium-derived substances in the heart are closely linked, interrelated, and interactive. It may therefore be simplistic to try and define their properties independently from one another. Moreover, in relation specifically to the endocardial endothelium, an active transendothelial physicochemical gradient for various ions, or blood-heart barrier, has been demonstrated. Linkage of this blood-heart barrier to the various other endothelium-mediated signaling pathways or to the putative vascular endothelium-derived hyperpolarizing factors remains to be determined. At the early stages of cardiac failure, all major cardiovascular risk factors may cause cardiac endothelial activation as an adaptive response often followed by cardiac endothelial dysfunction. Because of the interdependency of all endothelial signaling pathways, activation or disturbance of any will necessarily affect the others leading to a disturbance of their normal balance, leading to further progression of cardiac failure.

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Negative Chronotropic Effect of Endothelin 1 Mediated Through ET _A Receptors in Guinea Pig Atria

Cited by 38 publications

References 41 publications

Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Endothelin and the Ischaemic Heart

Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity

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Negative Chronotropic Effect of Endothelin 1 Mediated Through ET A Receptors in Guinea Pig Atria

Cited by 38 publications

References 41 publications

Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Endothelin-1 Regulates Cardiac L-Type Calcium Channels via NAD(P)H Oxidase-Derived Superoxide

Endothelin and the Ischaemic Heart

Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity

Contact Info

Product

Resources

About

Negative Chronotropic Effect of Endothelin 1 Mediated Through ET _A Receptors in Guinea Pig Atria