scholarly journals Sympathetic Nervous System Mediates Cardiac Remodeling After Myocardial Infarction in a Circadian Disruption Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuhong Wang ◽  
Wanli Jiang ◽  
Hu Chen ◽  
Huixin Zhou ◽  
Zhihao Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Pseudorabies Virus ◽  
Left Ventricular ◽  
Circadian Disruption ◽  
Empty Vector ◽  
Sympathetic Nervous

Background: Circadian rhythms have a considerable impact on the daily physiology of the heart, and their disruption causes pathology. Several studies have revealed that circadian disruption impaired cardiac remodeling after myocardial infarction (MI); however, the underlying brain-heart mechanisms remain unknown. We aim to discuss whether circadian disruption facilitates cardiac remodeling after MI by activating sympathetic nervous system.Methods: Rats were randomly divided into three groups: Sham group (Sham), MI group (MI), and MI+ circadian disruption group (MI+Dis); rats were treated with pseudorabies virus (PRV) injections for trans-synaptic retrograde tracing; rats were randomly divided into two groups: MI+ circadian disruption + Empty Vector+ clozapine N-oxide (CNO) (Empty Vector), and MI+ circadian disruption + hM4D(Gi)+ CNO [hM4D(Gi)].Results: Circadian disruption significantly facilitated cardiac remodeling after MI with lower systolic function, larger left ventricular volume, and aggravated cardiac fibrosis. Cardiac sympathetic remodeling makers and serum norepinephrine levels were also significantly increased by circadian disruption. PRV virus-labeled neurons were identified in the superior cervical ganglion (SCG), paraventricular nucleus (PVN), and suprachiasmatic nucleus (SCN) regions. Ganglionic blockade via designer receptors exclusively activated by designer drugs (DREADD) technique suppressed the activity of sympathetic nervous system and significantly alleviated the disruption-related cardiac dysfunction.Conclusion: Circadian disruption adversely affected cardiac remodeling after MI possibly by activating sympathetic nervous system, and suppressing sympathetic activity can attenuate this disruption-related cardiac dysfunction.

scholarly journals Endothelial NADPH oxidases protect against sympathetic nervous system hyperactivity-induced cardiac dysfunction and remodeling in mice: contribution of SGLT2

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Kerth ◽  
A Petry ◽  
D Kracun ◽  
V B Schini-Kerth ◽  
A Goerlach
Keyword(s):  
Endothelial Cells ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Nadph Oxidase ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Wild Type ◽  
Nadph Oxidases ◽  
Oxidase Subunit ◽  
Sympathetic Nervous

Abstract Background NADPH oxidase-derived reactive oxygen species (ROS) contribute to cardiac dysfunction, often characterized by coronary microvascular dysfunction, an inflammatory response and cardiomyocyte hypertrophy. Hyperactivity of the sympathetic nervous system (SNS) induces oxidative stress, promoting cardiac dysfunction and the development of heart failure. Selective inhibitors of sodium-glucose co-transporter 2 (SGLT2), have shown remarkable cardioprotective effects in clinical studies. Recently, SGLT2 inhibitors have been reported to prevent endothelial dysfunction and pro-inflammatory responses in endothelial cells in response to angiotensin II involving NADPH oxidases. Purpose Therefore, the aim of the study was to determine whether endothelial NADPH oxidases promote SNS-induced cardiac dysfunction and to clarify the role of SGLT2. Methods Male wild-type mice and mice lacking the NADPH oxidase subunit p22phox in the endothelium (p22phox ecKO, 11-week-old) were treated with isoproterenol (100 mg/kg) for five consecutive days and sacrificed at day 14. Hemodynamic measurements of left (LV) and right (RV) ventricles were performed by a transthoracic approach. Heart tissue sections were stained with Sirius red to evaluate fibrosis and wheat germ agglutinin to assess cardiomyocyte size. Cultured human microvascular endothelial cells (HMEC-1) were stimulated with 100 nM isoproterenol and ROS levels were assessed by dihydroethidium fluorescence. The expression level of target genes and proteins was assessed by quantitative real-time PCR and Western blot, respectively. siRNA approaches were used to down-regulate either the NADPH oxidase subunit p22phox or SGLT2. Results The isoproterenol treatment increased LV and RV systolic pressures in wild-type mice but not in p22phox ecKO mice. p22phox ecKO mice were protected against isoproterenol-induced fibrosis, cardiac remodeling characterized by upregulation of mRNA levels of ANP, BNP and β-MHC, and pulmonary congestion. LV remodeling was associated with upregulation of the NADPH oxidase subunits p22phox, Nox2, and Nox4 as well as of SGLT2 in wild-type mice, however no such effects were observed in p22phox ecKO mice. Exposure of HMEC-1 to isoproterenol stimulated the formation of ROS and caused an upregulation of p22phox and SGLT2 protein levels in a time- and concentration-dependent manner. No such effects were observed following silencing of either p22phox or SGLT2, or use of a selective SGLT2 inhibitor. Conclusion Deletion of the NADPH oxidase subunit p22phox in the endothelium protected against SNS hyperactivity induced LV cardiac dysfunction and remodeling, and prevented upregulation of SGLT2. Since depletion of SGLT2 prevented the pro-oxidant response to isoproterenol in endothelial cells, the endothelial NADPH oxidase/SGLT2 pathway seems to have a prominent role in promoting cardiac remodeling and dysfunction in SNS hyperactivity. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Deutsches Herzzentrum München

CNS origins of the sympathetic nervous system outflow to brown adipose tissue

1999 ◽  
Vol 276 (6) ◽  
pp. R1569-R1578 ◽  
Author(s):  
Maryam Bamshad ◽  
C. Kay Song ◽  
Timothy J. Bartness
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Sympathetic Nervous System ◽  
Brown Adipose Tissue ◽  
Pseudorabies Virus ◽  
Critical Role ◽  
Hypothalamic Nucleus ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Diet Induced Thermogenesis

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.

scholarly journals MicroRNAs Regulating Renin–Angiotensin–Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1771
Author(s):  
Alex Cleber Improta-Caria ◽  
Marcela Gordilho Aras ◽  
Luca Nascimento ◽  
Ricardo Augusto Leoni De Sousa ◽  
Roque Aras-Júnior ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Left Ventricular Hypertrophy ◽  
Signaling Pathways ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Gene And Protein Expression ◽  
Sympathetic Nervous

MicroRNAs are small non-coding RNAs that regulate gene and protein expression. MicroRNAs also regulate several cellular processes such as proliferation, differentiation, cell cycle, apoptosis, among others. In this context, they play important roles in the human body and in the pathogenesis of diseases such as cancer, diabetes, obesity and hypertension. In hypertension, microRNAs act on the renin–angiotensin–aldosterone system, sympathetic nervous system and left ventricular hypertrophy, however the signaling pathways that interact in these processes and are regulated by microRNAs inducing hypertension and the worsening of the disease still need to be elucidated. Thus, the aim of this review is to analyze the pattern of expression of microRNAs in these processes and the possible associated signaling pathways.

scholarly journals Cardiovascular Risk in Chronic Kidney Disease: Role of the Sympathetic Nervous System

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jeanie Park
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Nervous System ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Renal Disease ◽  
Left Ventricular ◽  
Sympathetic Nervous

Patients with chronic kidney disease are at significantly increased risk for cardiovascular disease and sudden cardiac death. One mechanism underlying increased cardiovascular risk in patients with renal failure includes overactivation of the sympathetic nervous system (SNS). Multiple human and animal studies have shown that central sympathetic outflow is chronically elevated in patients with both end-stage renal disease (ESRD) and chronic kidney disease (CKD). SNS overactivation, in turn, increases the risk of cardiovascular disease and sudden death by increasing arterial blood pressure, arrythmogenicity, left ventricular hypertrophy, and coronary vasoconstriction and contributes to the progression renal disease. This paper will examine the evidence for SNS overactivation in renal failure from both human and experimental studies and discuss mechanisms of SNS overactivity in CKD and therapeutic implications.

ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN CARDIAC REMODELING IN HYPERTENSION

2001 ◽  
Vol 23 (1-2) ◽  
pp. 35-43 ◽  
Author(s):  
Guido Iaccarino ◽  
Emanuele Barbato ◽  
Ersilia Cipoletta ◽  
Antonia Fiorillo ◽  
Bruno Trimarco
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Remodeling ◽  
Sympathetic Nervous

Temporal changes in left ventricular function after massive sympathetic nervous system activation

1994 ◽  
Vol 72 (6) ◽  
pp. 693-700 ◽  
Author(s):  
Sally A. Lang ◽  
Michael B. Maron ◽  
Frank J. Bosso ◽  
Charles F. Pilati
Keyword(s):  
Nervous System ◽  
Left Ventricle ◽  
Sympathetic Nervous System ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Neurogenic Pulmonary Edema ◽  
Plasma Catecholamine ◽  
Stroke Work ◽  
Sympathetic Nervous

Intense activation of the sympathetic nervous system (SNS) decreases the contractile state of the rabbit left ventricle (LV). In this study, we determined the time course of LV dysfunction after massive central activation of the SNS in dogs. Veratrine (40–80 μg/kg) was injected intracisternally to activate the SNS in six chloralose-anesthetized dogs, and LV end-diastolic pressure (LVEDP), cardiac output, heart rate, and aortic pressure (Pa) were measured at 30-min intervals for 3 h. Pa increased from 147 ± 8 (SE) to 272 ± 7 mmHg (1 mmHg = 133.3 Pa) within 15 min, then declined to 148 ± 16 mmHg by 1 h. LV function curves (stroke work versus LVEDP or stroke work versus LV transmural pressure) showed a marked decrease in slope and a shift to the right within minutes after activating the SNS, which persisted for the duration of the experiment. These data indicate that LV contractility was diminished in these animals. No changes in LV function were observed in three dogs serving as time-matched controls. In three additional dogs, LV pressure was raised to a degree similar to that observed after SNS activation by constricting the ascending aorta for 1 h. These animals exhibited only modest shifts in the LV function curve during and after aortic constriction. Mean plasma catecholamine concentration increased by one to two orders of magnitude in animals after SNS activation, but only minor changes were observed in the other two groups. We conclude that myocardial contractility declines markedly soon after massive SNS activation and is not solely a function of the initial hypertensive period.Key words: left ventricle contractility, heart failure, neurogenic pulmonary edema, sympathetic nervous system, catecholamines, veratrine.

Role of catecholamines in the pathogenesis of diabetic cardiomyopathy

2019 ◽  
Vol 97 (9) ◽  
pp. 815-819 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
Pallab K. Ganguly ◽  
Sukhwinder K. Bhullar ◽  
Paramjit S. Tappia
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Oxidation Products ◽  
Sympathetic Nervous ◽  
Myocardial Gene Expression

Although the sympathetic nervous system plays an important role in the regulation of cardiac function, the overactivation of the sympathetic nervous system under stressful conditions including diabetes has been shown to result in the excessive production of circulating catecholamines as well as an increase in the myocardial concentration of catecholamines. In this brief review, we provide some evidence to suggest that the oxidation products of catecholamines such as aminochrome and oxyradicals, lead to metabolic derangements, Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+, as well as activation of proteases and changes in myocardial gene expression. These alterations due to elevated levels of circulatory catecholamines are associated with oxidative stress, subcellular remodeling, and the development of cardiac dysfunction in chronic diabetes.

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