CHANGES IN VASCULAR ALPHA-ADRENERGIC RECEPTOR MECHANISMS DURING MATURATION.

Persistent Link:
http://hdl.handle.net/10150/184325
Title:
CHANGES IN VASCULAR ALPHA-ADRENERGIC RECEPTOR MECHANISMS DURING MATURATION.
Author:
BANNER, WILLIAM, JR.
Issue Date:
1982
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:
The premature infant is subject to pathological alterations of the cardiovascular system leading to insufficient pulmonary blood flow and/or sudden surges of pressure to fragile cerebral blood vessels, conditions which are often associated with hypotension. Dobutamine appears to be a potentially useful agent to increase pulmonary blood flow and correct hypotension. In view of this potential, the alpha-adrenergic characteristics of dobutamine acts were studied in the isolated rabbit femoral and pulmonary arteries. Dobutamine on the post synaptic membrane of these tissues as a high affinity, low intrinsic activity alpha adrenergic agonist. No action of dobutamine to modulate stimulation evoked release of norepinephrine was found, although dobutamine did increase spontaneous release of norepinephrine. This effect was not blocked by antagonists of uptake 1 and uptake 2. To further evaluate dobutamine for use in the neonate, contractile responses of the femoral and pulmonary arteries and aorta to dobutamine and norepinephrine were studied in dogs of various ages from newborn to 6 weeks. Maximal contractile responses to norepinephrine in the pulmonary artery and aorta increased with age. Dobutamine produced small or no responses in all newborn tissues studied and also showed increasing responsiveness with age. To allow future study of the mechanism of these changes a method of radioligand binding was established for vascular smooth muscle using the ligands prazosin and rauwolscine in the dog and rabbit pulmonary artery and aorta. This binding was found to demonstrate the properties of saturability, sterospecificity and rank order of potency. Possible variables that could account for the observed changes in response during maturation were mathematically modeled to provide a theoretical basis for future studies combining measurement of contractile response and radioligand binding techniques.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dobutamine -- Physiological effect.; Adrenergic mechanisms.; Newborn infants -- Effect of drugs on.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology; Graduate College
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleCHANGES IN VASCULAR ALPHA-ADRENERGIC RECEPTOR MECHANISMS DURING MATURATION.en_US
dc.creatorBANNER, WILLIAM, JR.en_US
dc.contributor.authorBANNER, WILLIAM, JR.en_US
dc.date.issued1982en_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.abstractThe premature infant is subject to pathological alterations of the cardiovascular system leading to insufficient pulmonary blood flow and/or sudden surges of pressure to fragile cerebral blood vessels, conditions which are often associated with hypotension. Dobutamine appears to be a potentially useful agent to increase pulmonary blood flow and correct hypotension. In view of this potential, the alpha-adrenergic characteristics of dobutamine acts were studied in the isolated rabbit femoral and pulmonary arteries. Dobutamine on the post synaptic membrane of these tissues as a high affinity, low intrinsic activity alpha adrenergic agonist. No action of dobutamine to modulate stimulation evoked release of norepinephrine was found, although dobutamine did increase spontaneous release of norepinephrine. This effect was not blocked by antagonists of uptake 1 and uptake 2. To further evaluate dobutamine for use in the neonate, contractile responses of the femoral and pulmonary arteries and aorta to dobutamine and norepinephrine were studied in dogs of various ages from newborn to 6 weeks. Maximal contractile responses to norepinephrine in the pulmonary artery and aorta increased with age. Dobutamine produced small or no responses in all newborn tissues studied and also showed increasing responsiveness with age. To allow future study of the mechanism of these changes a method of radioligand binding was established for vascular smooth muscle using the ligands prazosin and rauwolscine in the dog and rabbit pulmonary artery and aorta. This binding was found to demonstrate the properties of saturability, sterospecificity and rank order of potency. Possible variables that could account for the observed changes in response during maturation were mathematically modeled to provide a theoretical basis for future studies combining measurement of contractile response and radioligand binding techniques.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDobutamine -- Physiological effect.en_US
dc.subjectAdrenergic mechanisms.en_US
dc.subjectNewborn infants -- Effect of drugs on.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.committeememberKreulenen_US
dc.contributor.committeememberYamamuraen_US
dc.contributor.committeememberPerrieren_US
dc.contributor.committeememberMayersohnen_US
dc.identifier.proquest8227338en_US
dc.identifier.oclc682927888en_US
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