Persistent Link:
http://hdl.handle.net/10150/187698
Title:
REGULATION OF MYOCARDIAL HYPERTROPHY BY EPINEPHRINE (HEART).
Author:
LARSON, DOUGLAS FRANK.
Issue Date:
1984
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Hormonal regulation of growth and of macromolecular synthesis in a variety of tissues is now well established. This dissertation addresses the role of circulating hormones, particularly epinephrine, in the physiological regulation of myocardial mass. Following hemodynamic overload of the right ventricle, the circulating epinephrine concentration increased significantly, and blood epinephrine exhibited a significant positive correlation with myocardial mass. Further, a nonspecific β-antagonist, propranolol, blocked the usual myocardial hypertrophy that occurs in response to hemodynamic overload. These studies strongly implicate β-adrenoceptors in the regulation of myocardial mass. Theoretically, a circulating myocardial trophic hormone should result in biventricular hypertrophy. We found that a selective hemodynamic overload of the right ventricle produced significant hypertrophy of both the right and the left ventricles. A biochemical marker of β-receptor activity, ornithine decarboxylase, a key regulatory enzyme in growth, showed elevated activity in both the right and left ventricles following hemodynamic overload of the left ventricle. To further evaluate possible circulating myocardial trophic hormones, we studied hypertrophy in a donor heart transplanted into the abdomen of a recipient animal. Myocardial hypertrophy of the donor heart occurred independently of innervation and of any hemodynamic parameters. Alteration in myocardial mass paralleled the extent of β-receptor activity as assessed by the administration of exogenous β-agonists or by the modulation of β-receptor number by denervation. β-Receptor activity was assessed by the ability of isoproterenol to elevate ornithine decarboxylase activity in either the donor or the recipient heart. Finally, alterations in the levels of circulating endogenous hormones in response to pulmonary artery banding of the recipient rat heart resulted in concomitant hypertrophy of both recipient and donor hearts. These studies suggest that myocardial mass is regulated by the concentration of circulating epinephrine through its effect on myocardial β-adrenoceptors. This effect may be modified by the level of other hormones such as thyroid hormone, but does not appear to be altered to any extent by myocardial innervation or by the alteration of hemodynamic parameters except as they affect the circulating level of catecholamines.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Heart -- Hypertrophy -- Treatment.; Adrenaline -- Therapeutic use.; Adrenaline -- Physiological effect.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleREGULATION OF MYOCARDIAL HYPERTROPHY BY EPINEPHRINE (HEART).en_US
dc.creatorLARSON, DOUGLAS FRANK.en_US
dc.contributor.authorLARSON, DOUGLAS FRANK.en_US
dc.date.issued1984en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHormonal regulation of growth and of macromolecular synthesis in a variety of tissues is now well established. This dissertation addresses the role of circulating hormones, particularly epinephrine, in the physiological regulation of myocardial mass. Following hemodynamic overload of the right ventricle, the circulating epinephrine concentration increased significantly, and blood epinephrine exhibited a significant positive correlation with myocardial mass. Further, a nonspecific β-antagonist, propranolol, blocked the usual myocardial hypertrophy that occurs in response to hemodynamic overload. These studies strongly implicate β-adrenoceptors in the regulation of myocardial mass. Theoretically, a circulating myocardial trophic hormone should result in biventricular hypertrophy. We found that a selective hemodynamic overload of the right ventricle produced significant hypertrophy of both the right and the left ventricles. A biochemical marker of β-receptor activity, ornithine decarboxylase, a key regulatory enzyme in growth, showed elevated activity in both the right and left ventricles following hemodynamic overload of the left ventricle. To further evaluate possible circulating myocardial trophic hormones, we studied hypertrophy in a donor heart transplanted into the abdomen of a recipient animal. Myocardial hypertrophy of the donor heart occurred independently of innervation and of any hemodynamic parameters. Alteration in myocardial mass paralleled the extent of β-receptor activity as assessed by the administration of exogenous β-agonists or by the modulation of β-receptor number by denervation. β-Receptor activity was assessed by the ability of isoproterenol to elevate ornithine decarboxylase activity in either the donor or the recipient heart. Finally, alterations in the levels of circulating endogenous hormones in response to pulmonary artery banding of the recipient rat heart resulted in concomitant hypertrophy of both recipient and donor hearts. These studies suggest that myocardial mass is regulated by the concentration of circulating epinephrine through its effect on myocardial β-adrenoceptors. This effect may be modified by the level of other hormones such as thyroid hormone, but does not appear to be altered to any extent by myocardial innervation or by the alteration of hemodynamic parameters except as they affect the circulating level of catecholamines.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHeart -- Hypertrophy -- Treatment.en_US
dc.subjectAdrenaline -- Therapeutic use.en_US
dc.subjectAdrenaline -- Physiological effect.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.identifier.proquest8415071en_US
dc.identifier.oclc691259062en_US
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