Immobilization Stress With &lt;i&gt;α&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

Kuroda, Ryo; Shintani-Ishida, Kaori; Unuma, Kana; Yoshida, Kenichi

doi:10.1536/ihj.15-034

Cited by 11 publications

(6 citation statements)

References 40 publications

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“…The supernatants were collected and evaluated using the malondialdehyde assay kit (Jiancheng Bioengineering Institute, Nanjing, China) according to the manufacturer's protocol. Echocardiography: Echocardiographic studies were performed as described previously, 31) using a high-resolution ultrasound system for rodents (Vevo770, VisualSonics Inc, Ontario, Canada) under anesthesia with 1.5% isoflurane 7 days after establishment of the animal models. To assess the function of the left ventricles, left ventricular end-diastolic diameter (LVDd), LV anterior wall thickness (LVAWth), and ejection fraction (LVEF) were calculated.…”

Section: Methodsmentioning

confidence: 99%

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

Huang

Zhang

et al. 2017

Int. Heart J.

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SummaryHexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 μg/kg·day], ghrelin [400 μg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1β, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist A cute myocardial infarction, which is caused by a sudden embolism of the coronary arteries, is a leading cause of mortality. As the primary clinical therapy for treatment of myocardial infarction, myocardial reperfusion can also aggravate cardiac injury. 1) Its mechanism includes calcium overload, cardiomyocyte apoptosis, and reactive oxygen species (ROS) accumulation.2-5) Finding a strategy to alleviate myocardial I/R injury has become a hot research field in cardiology.In vivo I/R models can cause regional myocardial I/R injury by ligating the left anterior descending coronary artery, which have been widely used to mimic the process of myocardial infarction and subsequent reperfusion.6) Compared to the in vitro global I/R models, in vivo I/R models can not only reveal changes in hemodynamics, and cardiac structure and function after I/R, but also display the impact of molecules in reperfusion flow on I/R myocardium, such as ROS and inflammation cytokines.7) The in vivo I/R models are more consistent with the pathophysiological process of myocardial I/R injury.Ghrelin, a growth hormone-releasing peptide produced in the stomach, is an endogenous ligand of growth hormone secretagogue receptor (GHSR) 1a. Previous studies have demonstrated the cardioprotective effects of exogenous ghrelin administration. 8) Hexarelin, a synthetic analog of ghrelin, shows effects similar to those of ghrelin and is more chemically stable, making it a potential alternative to ghrelin. Its beneficial action on the cardiovascular system has been reported by a lot of research, including inhibition of cardiomyocyte apoptosis, [9][10][11] anti-atherosclerosis, 12,13) impro...

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Section: Methodsmentioning

confidence: 99%

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

Huang

Zhang

et al. 2017

Int. Heart J.

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“…In recent years, some researchers have already used animal models treated with high doses of catecholamines or adrenoceptor agonists or immobilization (IMO) to stimulate some or all of the abovementioned clinical manifestations of TTS. IMO in rats was used to study psychological stress, which is a successful model of TTS in rats [152][153][154][182][183][184][185][186][187]. IMO in rats triggered a transient and reversible reduction of LV contraction, including LV apical ballooning prevented by pretreatment with an adrenoceptor blocker, suggesting that the activation of β1 adrenergic receptors in the heart and the activation of α1 adrenergic receptors in the aorta are the primary cause of TTS [183,188,189].…”

Section: Animal Models and Mechanistic Studiesmentioning

confidence: 99%

“…Nevertheless, an α-adrenergic blockade reduced the development of the adrenaline-induced cardiac basal lesion but did not affect the structural and functional alterations [194]. Importantly, epinephrine-specific β2AR-G(i) signaling may have evolved as a cardioprotective strategy to limit catecholamine-induced myocardial toxicity during acute stress, while α2AR/Gi-dependent signaling attenuates myosin-binding protein-C (MyBP-C) phosphorylation and contractility in the anterior wall (AW) through an epinephrine surge in TTS rats [16,182]. However, no statistically significant difference of the β2AR-dependent cAMP levels was observed between the apical and basal cells [191].…”

Section: Animal Models and Mechanistic Studiesmentioning

confidence: 99%

“…The animal models of TTS are mainly based on monkeys, rabbits, rats and mice, which can be used to simulate TTS to a certain extent through immobilization, repeated intravenous infusion of an epinephrine overdose, vagal stimulation, intraperitoneally isoprenaline and other methods [152][153][154][182][183][184][185][186][187][188][190][191][192][193][194][195][197][198][199][200][201][202][203][204][205][206]. Many live-stranded cetaceans and terrestrial wildlife experienced capture myopathy, which was similar to TTS [207,208].…”

Section: Animal Models and Mechanistic Studiesmentioning

confidence: 99%

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Takotsubo Syndrome: Translational Implications and Pathomechanisms

Fan

Yang

Kowitz

et al. 2022

IJMS

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Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.

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“…2 ). The α 2 -AR agonist, xylazine, when administered to immobilized rats, has been shown to impair cardiac contractility, which eliminates pertussis toxin [ 136 ]. Isoproterenol (50 mg/kg intraperitoneally) was found to cause the appearance of akinetic regions in the left ventricle of rats 60 min after injection [ 137 ].…”

Section: Pathogenesis Of Stress Cardiomyopathymentioning

confidence: 99%

Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis

Прокудина

Kurbatov

Zavadovsky

et al. 2021

CCR

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: The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart, lack of coronary artery obstruction, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.6 - 2.5% of patients with acute coronary syndrome. The occurrence of takotsubo syndrome is 9 times higher in women, who are aged 60-70 years old , than in men. The hospital mortality among patients with TS corresponds to 3.5% - 12%. In many patients with TS, but not in all, physical or emotional stress precedes the disease. Many patients with TS, but not all, have neurological or mental illnesses. The level of catecholamines is increased in patients with TS, therefore, the occurrence of TS is associated with the excessive activation of the adrenergic system. The negative inotropic effect of catecholamines is associated with the activation of β2 adrenergic receptors. An important role of the adrenergic system in the pathogenesis of TS is confirmed by studies which were performed using 125I-metaiodobenzylguanidine (125I –MIBG). TS causes edema and inflammation of the myocardium. The inflammatory response in TS is systemic. TS causes impaired coronary microcirculation and reduces coronary reserve. There is reason to believe that an increase in blood viscosity may play an important role in the pathogenesis of microcirculatory dysfunction in patients with TS. Epicardial coronary artery spasm is not obligatory for the occurrence of TS. Cortisol, endothelin-1 and microRNAs are challengers for the role of TS triggers. A decrease in estrogen levels is a factor contributing to the onset of TS. The central nervous system appears to play an important role in the pathogenesis of TS.

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Immobilization Stress With <i>α</i><sub>2</sub>-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

Cited by 11 publications

References 40 publications

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis

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