Effects of treprostinil sodium in a monocrotaline-induced rat model of pulmonary hypertension

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Effects of treprostinil sodium in a monocrotaline-induced rat model of pulmonary hypertension

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/4288

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dc.contributor.advisor Skimming, Jeffrey W. en
dc.contributor.advisor DeMarco, Vincent G. en
dc.contributor.author Latcham, Shena L., 1978- en_US
dc.date.accessioned 2010-01-12T16:46:25Z
dc.date.available 2010-01-12T16:46:25Z
dc.date.issued 2005 en_US
dc.date.submitted 2005 Spring en
dc.identifier.other LatchamS-081805-T2260 en_US
dc.identifier.uri http://hdl.handle.net/10355/4288
dc.description "May 2005" en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- microbiology (Medicine). en_US
dc.description Includes bibliographical references. en_US
dc.description Vita. en_US
dc.description The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. en_US
dc.description Thesis (M.S.) University of Missouri-Columbia 2005. en_US
dc.description.abstract Treprostinil is a prostacyclin analog currently used in the treatment of pulmonary hypertension. Although clinical studies show treprostinil to be a successful therapy for pulmonary hypertension, little information exists concerning the effects of treprostinil treatment in vivo. The purpose of this study is to elucidate the effects of treprostinil on right ventricular systolic pressure (RVSP), right ventricular hypertrophy and vascular remodeling in a rat model of MCT-induced pulmonary hypertension. Male, Sprague-Dawley rats were randomized to one of four treatment groups; control, monocrotaline (MCT) only, MCT with treprostinil treatment (MCT/TRE), and treprostinil treatment only (TRE). At the beginning of the experiment, rats received a one-time subcutaneous dose of MCT (60 mg/kg) or saline. Rats were then administered either treprostinil or placebo for 28-days. After 28-days of treprostinil treatment, we recorded RVSP and right ventricular size. In addition, paraffin embedded left whole lung tissues were used for morphometric analysis and right whole lung tissues were snap frozen in liquid nitrogen for protein analysis. As expected, MCT exposure caused a significant increase in RVSP and right ventricular hypertrophy. Morphometric analyses also indicated that MCT-exposure led to medial wall thickening of the pulmonary vasculature. Neither low-dose (10 ng/kg/min) nor high-dose (150 ng/kg/min) treprostinil therapy attenuated elevations of RVSP and right ventricular hypertrophy in pulmonary hypertensive rats. In addition, there was no attenuation of medial wall thickening when MCT-exposed rats also received treprostinil treatment. Finally, treprostinil significantly lowered PPAR-[gamma] protein expression in MCT-exposed rats. In conclusion, we demonstrated that increases in RVSP, right ventricular hypertrophy and vascular remodeling associated with MCT-induced pulmonary hypertension are not attenuated with treprostinil therapy. Additionally, we found that treprostinil attenuated the induction of PPAR-[gamma] protein levels in whole lung homogenates of MCT-exposed rats. Although we have not yet established that PPAR-[gamma] is an important therapeutic target for pulmonary hypertension, we speculate that further investigation of its role could reveal a mechanism in which PGI₂ elicits its effects on the pulmonary vasculature. en_US
dc.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.relation.ispartof 2005 Freely available theses (MU) en_US
dc.subject.mesh Ventricular Pressure -- drug effects en_US
dc.subject.mesh Hypertension, Pulmonary -- drug therapy en_US
dc.subject.mesh Epoprostenol -- analogs & derivatives en_US
dc.subject.mesh Hypertrophy, Right Ventricular -- etiology en_US
dc.subject.mesh Models, Animal en_US
dc.title Effects of treprostinil sodium in a monocrotaline-induced rat model of pulmonary hypertension en_US
dc.type Thesis en_US
thesis.degree.discipline Microbiology (Medicine) en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name M.S. en_US
thesis.degree.level Masters en_US
dc.identifier.merlin .b55147355 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Theses. 2005 Theses


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