The applicant proposes to investigate the physiologic importance of the intrinsic cardiac nervous system. The applicant's principal objective is to identify the specific deficits within the intrinsic cardiac ganglia and at the myocyte receptor-effector synaptic junctions that occur subsequent to decentralization of the heart and/or adrenalectomy. For this purpose five specific aims have been defined.
Specific Aim 1. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support modifies basal nerve activity and synaptic interactions within the in vivo intrinsic cardiac ganglia in response to application of specific cholinergic and non-cholinergic agonists and antagonists.
Specific Aim 2. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support alters the membrane properties and synaptic efficacy of cardiac neurons. Using intracellular microelectrode techniques applied to in vitro whole mount intracardiac ganglia, somatic responses to specific cholinergic and non-cholinergic agonists and antagonists will be evaluated prior to and during electrical stimulation of interganglionic nerves.
Specific Aim 3. Using receptor autoradiography, to determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies specific cholinergic, adrenergic and angiotensin II receptor densities and distributions within the intrinsic cardiac ganglia or within the electrical and contractile tissues of the canine heart.
Specific Aim 4. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies signal transduction within cardiac myocytes.
Specific Aim 5. To determine if restoration of circulating catecholamines alleviates the cardiodepression associated with chronic adrenalectomy with and without concurrent prolonged loss of extrinsic nerve inputs to the heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058140-05
Application #
6184326
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1997-04-01
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
5
Fiscal Year
2000
Total Cost
$247,314
Indirect Cost
Name
East Tennessee State University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Johnson City
State
TN
Country
United States
Zip Code
37614
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Smith, F M; McGuirt, A S; Leger, J et al. (2001) Effects of chronic cardiac decentralization on functional properties of canine intracardiac neurons in vitro. Am J Physiol Regul Integr Comp Physiol 281:R1474-82
Smith, F M; McGuirt, A S; Hoover, D B et al. (2001) Chronic decentralization of the heart differentially remodels canine intrinsic cardiac neuron muscarinic receptors. Am J Physiol Heart Circ Physiol 281:H1919-30
Farrell, D M; Wei, C C; Tallaj, J et al. (2001) Angiotensin II modulates catecholamine release into interstitial fluid of canine myocardium in vivo. Am J Physiol Heart Circ Physiol 281:H813-22

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