The Effect of BAPN on Heart Structure and Function in the Angiotensin II Hypertensive Mouse

Persistent Link:
http://hdl.handle.net/10150/228476
Title:
The Effect of BAPN on Heart Structure and Function in the Angiotensin II Hypertensive Mouse
Author:
Roeder, Laura
Issue Date:
2012
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:
Lysyl oxidase (LOX) is the enzyme that mediates cross-linking between collagen and elastin molecules during cardiac remodeling, LOX expression and activity is upregulated in response to the mechanical stresses that occur during hypertension. The aim of this study was to investigate the role of lysl oxidase (LOX) changes in cardiac structure and mechanical function during angiotensin II (AngII) induced hypertension. C57 male mice were given the LOX suicide substrate: β-aminoproprionitrile (BAPN) in their drinking water (300mg/kg/d). On day 14 of BAPN treatment an osmotic pump of AngII (490ng/kg/hr) was implanted. Weekly echo measurements were gathered. 28 days after pump implantation cardiac tissue was harvested for various assays including, LOX enzymatic activity, hydroxyproline quantification, and histological analysis. AngII treated groups showed an increase LOX protein expression, LOX activity, collagen cross-linking, and total collagen content while ECHO results showed an up-regulation aortic velocity time integral (AoVTI) and LV mass and down regulation of E/E-A VTI. When BAPN was co administered with AngII there was an attenuation seen in all these areas. While AngII+BAPN treated mice showed a return of these parameters to normal control levels. These results provide evidence that Angiotensin II-Induced hypertension causes the overexpression of LOX. LOX's overstimulation has a major influence in the cardiac structure and function. Conversely both the structural and mechanical changes can be extenuated with administration of the LOX suicide substrate BAPN.
Type:
text; Electronic Thesis
Keywords:
Medical Pharmacology
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Medical Pharmacology
Degree Grantor:
University of Arizona
Advisor:
Larson, Doug

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe Effect of BAPN on Heart Structure and Function in the Angiotensin II Hypertensive Mouseen_US
dc.creatorRoeder, Lauraen_US
dc.contributor.authorRoeder, Lauraen_US
dc.date.issued2012-
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.abstractLysyl oxidase (LOX) is the enzyme that mediates cross-linking between collagen and elastin molecules during cardiac remodeling, LOX expression and activity is upregulated in response to the mechanical stresses that occur during hypertension. The aim of this study was to investigate the role of lysl oxidase (LOX) changes in cardiac structure and mechanical function during angiotensin II (AngII) induced hypertension. C57 male mice were given the LOX suicide substrate: β-aminoproprionitrile (BAPN) in their drinking water (300mg/kg/d). On day 14 of BAPN treatment an osmotic pump of AngII (490ng/kg/hr) was implanted. Weekly echo measurements were gathered. 28 days after pump implantation cardiac tissue was harvested for various assays including, LOX enzymatic activity, hydroxyproline quantification, and histological analysis. AngII treated groups showed an increase LOX protein expression, LOX activity, collagen cross-linking, and total collagen content while ECHO results showed an up-regulation aortic velocity time integral (AoVTI) and LV mass and down regulation of E/E-A VTI. When BAPN was co administered with AngII there was an attenuation seen in all these areas. While AngII+BAPN treated mice showed a return of these parameters to normal control levels. These results provide evidence that Angiotensin II-Induced hypertension causes the overexpression of LOX. LOX's overstimulation has a major influence in the cardiac structure and function. Conversely both the structural and mechanical changes can be extenuated with administration of the LOX suicide substrate BAPN.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
dc.subjectMedical Pharmacologyen_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Pharmacologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLarson, Dougen_US
dc.contributor.committeememberVanderah, Todden_US
dc.contributor.committeememberPalmer, Johnen_US
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