Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice

2002 ◽  
Vol 283 (5) ◽  
pp. H1838-H1845 ◽  
Author(s):  
Patricia C. Brum ◽  
Jon Kosek ◽  
Andrew Patterson ◽  
Daniel Bernstein ◽  
Brian Kobilka
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Function ◽  
Knockout Mice ◽  
Cardiac Tissue ◽  
Cardiac Contractility ◽  
Peak Oxygen Uptake ◽  
Sympathetic Tone ◽  
Relevant Animal Model ◽  
Sympathetic Nervous

α2A-Adrenergic receptors (ARs) in the midbrain regulate sympathetic nervous system activity, and both α2A-ARs and α2C-ARs regulate catecholamine release from sympathetic nerve terminals in cardiac tissue. Disruption of both α2A- and α2C-ARs in mice leads to chronically elevated sympathetic tone and decreased cardiac function by 4 mo of age. These knockout mice have increased mortality, reduced exercise capacity, decreased peak oxygen uptake, and decreased cardiac contractility relative to wild-type controls. Moreover, we observed significant abnormalities in the ultrastructure of cardiac myocytes from α2A/α2C-AR knockout mice by electron microscopy. Our results demonstrate that chronic elevation of sympathetic tone can lead to abnormal cardiac function in the absence of prior myocardial injury or genetically induced alterations in myocardial structural or functional proteins. These mice provide a physiologically relevant animal model for investigating the role of the sympathetic nervous system in the development and progression of heart failure.

Abstract 360: MiR-133 Modulates the Beta1-Adrenergic Receptor Transduction Cascade

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Alessandra Castaldi ◽  
Tania Zaglia ◽  
Vittoria Di Mauro ◽  
Pierluigi Carullo ◽  
Giacomo Viggiani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Function ◽  
Cardiac Contractility ◽  
Experimental Studies ◽  
Mrna Translation ◽  
Loss Of Function ◽  
Sympathetic Nervous

Rationale: The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, over-activation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors (βARs) in cardiomyocytes (CMs) and lead to increased heart rate and cardiac contractility. However, chronic stimulation of βARs leads to impaired cardiac function and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MiR-133 is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of mRNA translation/stability. Objective: To determine whether miR-133 affects βAR signaling during progression to heart failure. Methods and Results: Based on bioinformatic analysis, β1AR and other components of the β1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A (PKA), were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult CMs following selective β1AR stimulation. Furthermore, gain- and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β1AR stimulation. This was confirmed in vivo using a novel cardiacspecific TetON-miR-133 inducible transgenic mouse model (Tg133). When subjected to transaortic constriction, Tg133 mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared to control mice. Conclusions: MiR-133 controls multiple components of the β1AR transduction cascade and is cardioprotective during heart failure.

Abnormal Regulation of the Sympathetic Nervous System in α2A-Adrenergic Receptor Knockout Mice

1999 ◽  
Vol 56 (1) ◽  
pp. 154-161 ◽  
Author(s):  
John D. Altman ◽  
Anne U. Trendelenburg ◽  
Leigh MacMillan ◽  
Dan Bernstein ◽  
Lee Limbird ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Knockout Mice ◽  
Adrenergic Receptor ◽  
Sympathetic Nervous

scholarly journals Rapid measurement of cardiac neuropeptide dynamics by capacitive immunoprobe in the porcine heart

2021 ◽  
Vol 320 (1) ◽  
pp. H66-H76
Author(s):  
Nicholas Kluge ◽  
Michael Dacey ◽  
Joseph Hadaya ◽  
Kalyanam Shivkumar ◽  
Shyue-An Chan ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Function ◽  
Neuropeptide Y ◽  
Cardiac Remodeling ◽  
Beating Heart ◽  
Porcine Heart ◽  
Rapid Measurement ◽  
Sympathetic Nervous

The sympathetic nervous system regulates cardiac function through release of neurotransmitters and neuropeptides within the myocardium. Neuropeptide Y (NPY) acts as an acute cardiac vasoconstrictor and chronically to regulate angiogenesis and cardiac remodeling. Current methodologies for the measure of NPY are not capable of providing rapid readouts on a single-sample basis. Here we provide the first in vivo methodology to report dynamic, localized NPY levels within both myocardium and vascular compartments in a beating heart.

scholarly journals The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity

2008 ◽  
Vol 183 (7) ◽  
pp. 1235-1242 ◽  
Author(s):  
Eiichi Hinoi ◽  
Nan Gao ◽  
Dae Young Jung ◽  
Vijay Yadav ◽  
Tatsuya Yoshizawa ◽  
...  
Keyword(s):  
Nervous System ◽  
Insulin Secretion ◽  
Sympathetic Nervous System ◽  
Glucose Intolerance ◽  
Glucose Homeostasis ◽  
Sympathetic Tone ◽  
Extracellular Signals ◽  
Sympathetic Nervous ◽  
The Relationship

The osteoblast-secreted molecule osteocalcin favors insulin secretion, but how this function is regulated in vivo by extracellular signals is for now unknown. In this study, we show that leptin, which instead inhibits insulin secretion, partly uses the sympathetic nervous system to fulfill this function. Remarkably, for our purpose, an osteoblast-specific ablation of sympathetic signaling results in a leptin-dependent hyperinsulinemia. In osteoblasts, sympathetic tone stimulates expression of Esp, a gene inhibiting the activity of osteocalcin, which is an insulin secretagogue. Accordingly, Esp inactivation doubles hyperinsulinemia and delays glucose intolerance in ob/ob mice, whereas Osteocalcin inactivation halves their hyperinsulinemia. By showing that leptin inhibits insulin secretion by decreasing osteocalcin bioactivity, this study illustrates the importance of the relationship existing between fat and skeleton for the regulation of glucose homeostasis.

scholarly journals HIF-1α is required for development of the sympathetic nervous system

2019 ◽  
Vol 116 (27) ◽  
pp. 13414-13423 ◽  
Author(s):  
Romana Bohuslavova ◽  
Radka Cerychova ◽  
Frantisek Papousek ◽  
Veronika Olejnickova ◽  
Martin Bartos ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Molecular Mechanisms ◽  
Cardiac Development ◽  
Sympathetic Innervation ◽  
Cardiac Contractility ◽  
Hypoxia Inducible Factor ◽  
Left Ventricular ◽  
Conditional Knockout ◽  
Sympathetic Nervous

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

scholarly journals Relationship between cardiac function and the sympathetic nervous system during exercise in patients with essential hypertension.

1988 ◽  
Vol 52 (10) ◽  
pp. 1121-1131 ◽  
Author(s):  
MITSUTAKA YASUDA ◽  
TOSHIO NISHIKIMI ◽  
KANAME AKIOKA ◽  
MASAKAZU TERAGAKI ◽  
HISAO OKU ◽  
...  
Keyword(s):  
Nervous System ◽  
Essential Hypertension ◽  
Sympathetic Nervous System ◽  
Cardiac Function ◽  
Sympathetic Nervous
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