scholarly journals Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload

2009 ◽  
Vol 297 (3) ◽  
pp. R859-R866 ◽  
Author(s):  
Jean C. Hardwick ◽  
Caitlin N. Baran ◽  
E. Marie Southerland ◽  
Jeffrey L. Ardell
Keyword(s):  
Guinea Pig ◽  
Neural Control ◽  
Neuronal Excitability ◽  
Pressure Overload ◽  
Immunohistochemical Analysis ◽  
Membrane Properties ◽  
Control Mechanisms ◽  
Pituitary Adenylate Cyclase ◽  
Oxide Synthase ◽  
Passive Membrane Properties

Chronic pressure overload (PO) is associated with cardiac hypertrophy and altered autonomic control of cardiac function, in which the latter may involve adaptations in central and/or peripheral cardiac neural control mechanisms. To evaluate the specific remodeling of the intrinsic cardiac nervous system following pressure overload, the descending thoracic aorta artery of the guinea pig was constricted ∼20%, and the animals recovered for 9 wk. Thereafter, atrial neurons of the intrinsic cardiac plexus were isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no significant changes in passive membrane properties or action potential depolarization compared with age-matched controls and sham-operated animals, but afterhyperpolarization duration was increased in PO animals. Neuronal excitability, as determined by the number of action potentials produced with depolarizing stimuli, was differentially increased in phasic neurons derived from PO animals in response to exogenously applied histamine compared with sham and age-matched controls. Conversely, pituitary adenylate cyclase-activating polypeptide-induced increases in intrinsic cardiac neuron evoked AP frequency were similar between control and PO animals. Immunohistochemical analysis demonstrated a twofold increase in the percentage of neurons immunoreactive for neuronal nitric oxide synthase in PO animals compared with control. The density of mast cells within the intrinsic cardiac plexus from PO animals was also increased twofold compared with preparations from control animals. These results indicate that congestive heart failure associated with chronic pressure overload induces a differential remodeling of intrinsic cardiac neurons and upregulation of neuronal responsiveness to specific neuromodulators.

scholarly journals Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus

2008 ◽  
Vol 295 (6) ◽  
pp. R1926-R1933 ◽  
Author(s):  
Jean C. Hardwick ◽  
E. Marie Southerland ◽  
Jeffrey L. Ardell
Keyword(s):  
Myocardial Infarction ◽  
Guinea Pig ◽  
Action Potential ◽  
Immunohistochemical Analysis ◽  
Membrane Properties ◽  
Chronic Myocardial Infarction ◽  
Guinea Pig Heart ◽  
Pituitary Adenylate Cyclase ◽  
Neurohumoral Control ◽  
Oxide Synthase

Chronic myocardial infarction (CMI) is associated with remodeling of the ventricle and evokes adaption in the cardiac neurohumoral control systems. To evaluate the remodeling of the intrinsic cardiac nervous system following myocardial infarction, the dorsal descending coronary artery was ligated in the guinea pig heart and the animals were allowed to recover for 7–9 wk. Thereafter, atrial neurons of the intrinsic cardiac plexus were isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no significant changes in passive membrane properties or action potential configuration compared with age-matched controls and sham-operated animals. The intrinsic cardiac neurons from chronic infarcted hearts did demonstrate an increase in evoked action potential (AP) frequency (as determined by the number of APs produced with depolarizing stimuli) and an increase in responses to exogenously applied histamine compared with sham and age-matched controls. Conversely, pituitary adenylate cyclase-activating polypeptide (PACAP)-induced increases in intrinsic cardiac neuron-evoked AP frequency were similar between control and CMI animals. Immunohistochemical analysis demonstrated a threefold increase in percentage of neurons immunoreactive for neuronal nitric oxide synthase (NOS) in CMI animals compared with control and the additional expression of inducible NOS by some neurons, which was not evident in control animals. Finally, the density of mast cells within the intrinsic cardiac plexus was increased threefold in preparations from CMI animals. These results indicate that CMI induces a differential remodeling of intrinsic cardiac neurons and functional upregulation of neuronal responsiveness to specific neuromodulators.

scholarly journals Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease

2012 ◽  
Vol 303 (9) ◽  
pp. R950-R958 ◽  
Author(s):  
Jean C. Hardwick ◽  
E. Marie Southerland ◽  
Allison E. Girasole ◽  
Shannon E. Ryan ◽  
Sara Negrotto ◽  
...  
Keyword(s):  
Heart Disease ◽  
Guinea Pig ◽  
Cardiac Disease ◽  
Neuronal Excitability ◽  
Cardiac Tissue ◽  
Pressure Overload ◽  
Dorsal Surface ◽  
Adrenergic Blockade ◽  
Disease States ◽  
Chronic Heart Disease

Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (∼20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg−1·day−1) or vehicle, for a total of 6–7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that β-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the β-receptors were more influential on remodeling during dynamic disease progression.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Expression and Modulation of Neuronal Excitability in Guinea Pig Cardiac Ganglia

1998 ◽  
Vol 18 (23) ◽  
pp. 9766-9779 ◽  
Author(s):  
Karen M. Braas ◽  
Victor May ◽  
Susan A. Harakall ◽  
Jean C. Hardwick ◽  
Rodney L. Parsons
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Neuronal Excitability ◽  
Cardiac Ganglia ◽  
Pituitary Adenylate Cyclase

scholarly journals Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

2011 ◽  
Vol 301 (5) ◽  
pp. H2093-H2101 ◽  
Author(s):  
Baptiste Kurtz ◽  
Helene B. Thibault ◽  
Michael J. Raher ◽  
John R. Popovich ◽  
Sharon Cawley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Insulin Resistance ◽  
Mitochondrial Respiration ◽  
Pressure Overload ◽  
Lv Remodeling ◽  
Stress Levels ◽  
Nitric Oxide Synthase 3 ◽  
And Function ◽  
Oxide Synthase

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.

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