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Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction
- Source :
- PLoS ONE, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, PLoS ONE, Vol 9, Iss 7, p e100179 (2014), Anatomy and Cell Biology Publications
- Publication Year :
- 2013
-
Abstract
- Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. alpha(2A)/alpha(2C)-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease.
- Subjects :
- Male
PROTEIN EXPRESSION
Physiology
Cholinergic Agents
lcsh:Medicine
Adrenergic
Gene Expression
Pharmacology
Cardiovascular Physiology
Biochemistry
Diagnostic Radiology
Parasympathetic nervous system
Mice
0302 clinical medicine
DEFICITS
Molecular Cell Biology
Ultrasound Imaging
Medicine and Health Sciences
Medicine
Myocytes, Cardiac
lcsh:Science
Cells, Cultured
Mice, Knockout
Mammals
0303 health sciences
Multidisciplinary
biology
Neurochemistry
Animal Models
CHRONIC HEART-FAILURE
RECEPTORS
medicine.anatomical_structure
Pyridostigmine
Echocardiography
Vertebrates
Blood Circulation
SURVIVAL
Anatomy
Neurochemicals
medicine.drug
Pyridostigmine Bromide
Signal Transduction
Research Article
medicine.medical_specialty
Cell Physiology
Cardiotonic Agents
Adrenergic receptor
Cardiology
EXERCISE
In Vitro Techniques
Autonomic Nervous System
Research and Analysis Methods
Rodents
RATS
Cell and Developmental Biology
03 medical and health sciences
Model Organisms
Diagnostic Medicine
Internal medicine
INSUFICIÊNCIA CARDÍACA
Genetics
Animals
VESICULAR ACETYLCHOLINE TRANSPORTER
Rats, Wistar
030304 developmental biology
Cholinesterase
Heart Failure
CARVEDILOL
business.industry
lcsh:R
Isoproterenol
Organisms
Biology and Life Sciences
Cell Biology
Rats
HYPERTROPHY
Mice, Inbred C57BL
Autonomic nervous system
Endocrinology
Cellular Neuroscience
biology.protein
Cardiovascular Anatomy
Cholinergic
lcsh:Q
Cholinesterase Inhibitors
business
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....104f9175fdad59880d43ea89693bb444