Reduction of Infarct Size by Selective Stimulation of Prostaglandin EP3Receptors in the Reperfused Ischemic Pig Heart

Hohlfeld, Thomas; Meyer-Kirchrath, Jutta; Vogel, Y.; Schrör, Karsten

doi:10.1006/jmcc.1999.1072

Cited by 46 publications

(34 citation statements)

References 32 publications

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“…14,15 The beneficial effects of prostaglandins release on the reperfusion arrhythmias appear to involve stimulation of EP 3 receptors, which in turn can induce activation of repolarizing membrane currents and inhibition of damages effects caused by ischemia-induced catecholamine release. 4 In summary, in the present study we have shown that at a low concentration, Ang-(1-7) decreased the incidence and duration of ischemia-reperfusion arrhythmias in isolated rat hearts. These cardioprotective effects were blocked by the Ang-(1-7) antagonist A-779.…”

Section: Discussionsupporting

confidence: 60%

“…[1][2][3][4][5] Besides angiotensin (Ang) II, other endogenous biologically active products of the RAS have been identified, including Ang-(1-7) and Ang- (3)(4)(5)(6)(7)(8). Among the biologically active end products of the RAS, the heptapeptide Ang-(1-7) is particularly interesting because it can be formed directly from Ang I by an ACE-independent pathway 6 and is essentially devoid of effects exerted by Ang II through AT 1 receptors, including vasoconstriction and induction of drinking.…”

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confidence: 99%

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Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

2001

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Abstract-In this study we evaluate the effects of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts. Rat hearts were perfused according to Langendorff technique and maintained in heated (37Ϯ1°C) and continuously gassed (95% O 2 /5% CO 2 ) Krebs-Ringer solution at constant pressure (65 mm Hg). The electrical activity was recorded with an ECG (bipolar). Local ischemia was induced by coronary ligation for 15 minutes. After ischemia, hearts were reperfused for 30 minutes. Cardiac arrhythmias were defined as the presence of ventricular tachycardia and/or ventricular fibrillation after the ligation of the coronary artery was released. Angiotensin II (0.20 nmol/L, nϭ10) produced a significant enhancement of reperfusion arrhythmias. On the other hand, Ang-(1-7) presented in the perfusion solution (0.22 nmol/L, nϭ11) reduced incidence and duration of arrhythmias. The antiarrhythmogenic effects of Ang-(1-7) was blocked by the selective Ang-(1-7) antagonist A-779 (2 nmol/L, nϭ9) and by indomethacin pretreatment (5 mg/kg IP, nϭ8) but not by the bradykinin B 2 antagonist HOE 140 (100 nmol/L, nϭ10) or by L-NAME pretreatment (30 mg/kg IP, nϭ8). These results suggest that the antiarrhythmogenic effect of low concentrations of Ang-(1-7) is mediated by a specific receptor and that release of endogenous prostaglandins .by Ang-(1-7) contributes to the alleviation of reversible and/or irreversible ischemia-reperfusion injury. Key Words: heart Ⅲ angiotensin II Ⅲ angiotensin antagonist Ⅲ renin-angiotensin system Ⅲ nitric oxide Ⅲ prostaglandins

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Section: Discussionsupporting

confidence: 60%

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confidence: 99%

Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

2001

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“…17 This discrepancy may result from the fact that some TP antagonists cross-act on other prostanoid receptors, such as EP 3 , 30 through which PGE 2 was reported to exert protective effects on cardiac I/R injury. 31 Another mechanism, that compensatory cardioprotective actions of PGI 2 may participate in the lack of effects of the TP deficiency, may be considered. This possibility is unlikely, however, because if PGI 2 were to show compensatory cardioprotective effects, the aggravating action of TXA 2 would be clearly detected in TP Ϫ/Ϫ mice as a decrease in the size of the infarct, which, however, was not detected in the present work.…”

Section: Discussionmentioning

confidence: 99%

Roles of Prostaglandin I ₂ and Thromboxane A ₂ in Cardiac Ischemia-Reperfusion Injury

et al. 2001

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Background-Prostaglandin (PG) I 2 and thromboxane (TX) A 2 , the most common prostanoids in the cardiovascular system, are produced abundantly during cardiac ischemia/reperfusion (I/R); their roles in I/R injury, however, remain undetermined. We intended to clarify these roles of PGI 2 and TXA 2 using mice lacking the PGI 2 receptor, IP Ϫ/Ϫ mice, or the TXA 2 receptor, TP Ϫ/Ϫ mice. Methods and Results-The left anterior descending coronary artery was occluded for 1 hour and then reperfused for 24hours. The size of myocardial infarct in IP Ϫ/Ϫ mice was significantly larger than that in wild-type mice, although the size of the area at risk was similar between the 2 groups of mice. In contrast, there was no such difference between TP

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“…40) Hohlfeld, et al demonstrated that the properties of EP3 include inhibition of adenylyl cyclase and upregulation during regional myocardial ischemia, suggesting an involvement in the antiischemic activity of PGE 2 and EP3. 41) To analyze the role of EP4 in the development of myocardial ischemia, we used a novel EP4 selective agonist called EP4RAG. Of note, EP4RAG significantly reduced the infarction per ischemic myocardium ratio and improved ventricular contraction compared to the vehicle treatment.…”

Section: Effects Of Ep 4 Agonists On Cardiovascular Disease I) Myocarmentioning

confidence: 99%

Roles of Prostaglandin E2 in Cardiovascular Diseases

et al. 2011

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SummaryProstaglandin E2 (PGE 2 ) is produced in inflammatory responses and regulates a variety of immunological reactions through 4 different receptor subtypes; EP1, 2, 3 and 4. However, the precise role of each receptor in cardiovascular disease has not yet been elucidated. Enhanced expression of some EPs has been observed in clinical and experimental cardiovascular diseases. EP agonists have been developed to clarify the role of each receptor. Recently, we developed a novel selective agonist to examine the effects of EP4 on cardiac transplantation, myocardial ischemia, and myocarditis. Of note, a selective EP4 agonist attenuated inflammatory cytokines and chemokines via attenuation of macrophage activation in inflammatory heart diseases. In this review article, we discuss the effects of PGE 2 receptor agonists on the development of cardiovascular diseases. (Int Heart J 2011; 52: 266-269) Key words: Prostaglandin, Receptors, Chemokine, Macrophage, Heart P rostanoids are known to be multifunctional physiologic factors. They are produced by various stimuli and participate in local homeostasis and physiologic responses. They are synthesized from arachidonic acid and quickly released to the extracellular medium to send signals via prostanoid receptors.1) The prostanoid receptors, DP, EP, FP, IP and TP, are bound to PGD 2 , PGE 2 , PGF 2α , PGI 2 , and TXA 2 , respectively. 2)In the cardiovascular system, these receptors are expressed on various cells, such as cardiomyocytes, vascular endothelium and smooth muscle cells.3) They play an important role in modulating homeostasis in the development of cardiovascular diseases, such as thrombosis and atherosclerosis.4) Recent studies revealed that prostanoids play an important role in both the occurrence and suppression of various cardiovascular diseases, such as myocardial ischemia, cardiac hypertrophy, cardiac fibrosis, and atherosclerosis. 5) However, the detailed roles of prostanoids in cardiovascular disease have not yet been completely elucidated. To clarify the mechanisms, selective receptor agonists have been developed.Among the prostanoids, PGE 2 is known to play a key role in the pathogenesis of cardiovascular diseases. It was reported that a deficiency of PGE 2 synthase-1 reduced plaque burden in fat-diet low-density lipoprotein receptor knockout mice.6) Another report revealed that PGE 2 synthase-1 knockout mice showed impaired left ventricular contraction after acute myocardial infarction.7) These studies indicate that PGE 2 plays a pivotal role in cardiovascular inflammation. 8, 9) PGE 2 exerts their effects via G-protein-coupled receptors, and PGE 2 -mediated cardioprotection is involved in the EP receptor subtypes. 10)Each receptor has their unique signaling pathways. EP1 couples to Gq and increases intracellular Ca . EP3 couples to Gi and inhibits the increase of cAMP. EP2 and EP4 receptors are coupled to stimulate adenylate cyclase, which leads to the elevation of intracellular cAMP.11) In these EP receptors, EP3 and EP4 are known to have cardioprote...

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Reduction of Infarct Size by Selective Stimulation of Prostaglandin EP3Receptors in the Reperfused Ischemic Pig Heart

Cited by 46 publications

References 32 publications

Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

Roles of Prostaglandin I ₂ and Thromboxane A ₂ in Cardiac Ischemia-Reperfusion Injury

Roles of Prostaglandin E2 in Cardiovascular Diseases

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Reduction of Infarct Size by Selective Stimulation of Prostaglandin EP3Receptors in the Reperfused Ischemic Pig Heart

Cited by 46 publications

References 32 publications

Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion

Roles of Prostaglandin I 2 and Thromboxane A 2 in Cardiac Ischemia-Reperfusion Injury

Roles of Prostaglandin E2 in Cardiovascular Diseases

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Roles of Prostaglandin I ₂ and Thromboxane A ₂ in Cardiac Ischemia-Reperfusion Injury