Different Contributions of Endothelin-A and Endothelin-B Receptors in Postischemic Cardiac Dysfunction and Norepinephrine Overflow in Rat Hearts

Yamamoto, Satoshi; Matsumoto, Noriko; Kanazawa, Mitsuo; Fujita, Marie; Takaoka, Masanori; Gariepy, Cheryl E.; Yanagisawa, Masashi; Matsumura, Yasuo

doi:10.1161/01.cir.0000153351.86708.f7

Cited by 40 publications

(57 citation statements)

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“…These findings were probably unexpected and contradict, in part, those reported 8 previously by the same group under identical experimental conditions; in this study, 8 endogenously generated and exogenously administered ET-1 evoked noradrenaline overflow and produced left ventricular dysfunction. The elegant study by Tawa et al raises several questions that were thoroughly addressed in their experiments.…”

Section: Pathophysiological Role Of Et-1contrasting

confidence: 77%

“…However, these effects diminished during subsequent phases (2-24 h) of evolving myocardial infarction. The data reported by Tawa et al, in context with previous work, 8,9 shed further light to a long-standing caveat on the role of the ETB receptor. Nevertheless, it should be emphasized that this information applies only to acute myocardial ischaemia and should not be extrapolated to other chronic disease states.…”

Section: Pathophysiological Role Of Et-1supporting

confidence: 66%

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Endothelin-1 during myocardial ischaemia: a double-edged sword?

Kolettis

2010

Hypertens Res

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Section: Pathophysiological Role Of Et-1contrasting

confidence: 77%

Section: Pathophysiological Role Of Et-1supporting

confidence: 66%

Endothelin-1 during myocardial ischaemia: a double-edged sword?

Kolettis

2010

Hypertens Res

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“…[7][8][9][10]14 In addition, we obtained evidence that exogenously applied ET-1 to the ischemic heart further enhanced the NE overflow and exacerbates the postischemic cardiac dusfunction. 10 In the present study, we expected that exogenously applied big ET-1 would cause deterioration of cardiac function following the global ischemia and reperfusion, because exogenously applied big ET-1 exerts qualitatively similar effects to ET-1, in the cardiovascular system in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 67%

“…Indeed, both selective ET A receptor antagonists and non-selective ET A /ET B receptor antagonists exhibited protective effects against the postischemic cardiac dysfunction. [7][8][9][10] Enhancement of cardiac sympathetic nerve activity and its consequent effect on norepinephrine (NE) overflow from the nerve endings has also been considered as a factor that aggravates cell damage in ischemic myocardium. 11 In fact, it has been demonstrated that the negative modulation of NE release significantly suppresses postischemic cardiac dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] We have found that endogenously generated ET-1 evokes NE overflow via the stimulation of ET A receptors, and this contributes to cardiac deterioration after ischemia/reperfusion. 6,10 Moreover, Isaka et al have demonstrated that both ET A and ET B receptors exist in the sympathetic nerve varicosities of guinea pig hearts, and modulate NE release in association with reperfusion arrhythmias. 14 Taken together, it is considered that endogenously generated ET-1 promotes postischemic NE overflow, and this is contributive, at least in part, to subsequent cardiac dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts

et al. 2010

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Endothelin-1 (ET-1) is involved in norepinephrine (NE) overflow and cardiac dysfunction after myocardial ischemia/reperfusion via the activation of ET A receptors. As ET-1 is generated from big ET-1 via endothelin-converting enzyme (ECE), ischemia/ reperfusion-induced cardiac injury may be exacerbated by exogenous big ET-1. The aim of this study was to investigate the influence of exogenously applied big ET-1 on ischemia/reperfusion-induced NE overflow and cardiac dysfunction. According to the Langendorff technique, isolated rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. Exogenous big ET-1 (0.1, 0.3 and 1 nM) was perfused, beginning 15 min before ischemia. Unexpectedly, higher doses (0.3 and 1 nM) of big ET-1 significantly improved indices of left ventricular function after ischemia/reperfusion, such as left ventricular developed pressure (LVDP), the maximum value of the first derivative of left ventricular pressure (dP/dt max ) and left ventricular end diastolic pressure (LVEDP). In addition, big ET-1 significantly suppressed excessive NE overflow in the coronary effluent from the postischemic heart. These effects of big ET-1 were markedly attenuated by treatment with SM-19712 (selective ECE inhibitor) or A-192621 (selective ET B receptor antagonist). On the other hand, those were not potentiated even though combined with ABT-627 (selective ET A receptor antagonist). From these findings, we suggest that exogenous big ET-1 has beneficial effects on ischemia/reperfusion-induced cardiac injury. It seems likely that big ET-1 is converted to ET-1, locally in the heart, and this ET-1 preferentially binds to ET B receptors to exert its related beneficial actions. Keywords: big endothelin-1; endothelin-1; ischemia/reperfusion; norepinephrine INTRODUCTION Endothelin-1 (ET-1) was originally found as a 21-amino-acid vasoconstrictor peptide produced by vascular endothelial cells. 1 This peptide is most abundant in the cardiovascular system, and at least two distinct ET receptors, ET A and ET B , have been identified. ET A receptors mediate vasoconstriction and cell proliferation, whereas ET B receptors are important for the clearance of ET-1, endothelial cell survival, the release of nitric oxide and prostacyclin. 2 There is accumulating evidence that ET-1 is closely related to the pathogenesis and development of several cardiovascular diseases. 3,4 It has been demonstrated that ischemia increases ET-1-binding sites in cardiac membranes. 5 In addition, we have recently noted that left ventricular ET-1 content is increased by ischemia/reperfusion in isolated rat hearts, and postischemic cardiac dysfunction is improved by suppressing the ET-1 biosynthesis. 6 These findings imply that endogenously generated ET-1 plays an important role in the pathophysiology of myocardial ischemia/reperfusion. Indeed, both selective

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Endothelin receptors, localized in sympathetic nerve terminals of the heart, modulate norepinephrine release and reperfusion arrhythmias

et al. 2006

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Endothelin (ET)-1 is an endogenous vasoconstrictor which modulates norepinephrine (NE) release in myocardial ischemia reperfusion. Recent studies have demonstrated the pro- or anti-arrhythmic effects in reperfusion. The present studies were undertaken to test the hypothesis that ET receptors located in sympathetic nerve terminals modulate NE release associated with reperfusion arrhythmias (ventricular fibrillation; VF). Immunohistochemical studies showed that both ETA and ETB receptors exist in the sympathetic nerve varicosities, which were stained positive for tyrosine hydroxylase (TH) in the left ventricular wall in guinea pigs. Isolated guinea pig hearts were subjected to 20 min of normothermic global ischemia followed by 30 min reperfusion. Exogenously applied ET-1 (0.1 and 1 nM) dose-dependently increased NE release and the duration of VF, but these responses were significantly suppressed with the Na(+)/H(+) exchanger inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride (10 microM). The ETA receptor antagonist (BQ123, 1 microM) and nonselective ET receptor antagonist (PD142893, 1 microM) significantly attenuated NE release and VF, whereas the ETB receptor antagonist (BQ788,300 nM) markedly elevated NE release but did not affect VF. These studies provide the first evidence that both ETA and ETB receptors, located in the sympathetic nerve varicosities, modulate NE release, at least in part, in association with reperfusion arrhythmias.

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Different Contributions of Endothelin-A and Endothelin-B Receptors in Postischemic Cardiac Dysfunction and Norepinephrine Overflow in Rat Hearts

Cited by 40 publications

References 46 publications

Endothelin-1 during myocardial ischaemia: a double-edged sword?

Endothelin-1 during myocardial ischaemia: a double-edged sword?

Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts

Endothelin receptors, localized in sympathetic nerve terminals of the heart, modulate norepinephrine release and reperfusion arrhythmias

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