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dc.contributor.advisorSkimming, Jeffrey W.eng
dc.contributor.advisorDeMarco, Vincent G.eng
dc.contributor.authorLatcham, Shena L., 1978-eng
dc.date.issued2005eng
dc.date.submitted2005 Springeng
dc.description"May 2005"eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- microbiology (Medicine).eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionThe 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.eng
dc.descriptionThesis (M.S.) University of Missouri-Columbia 2005.eng
dc.description.abstractTreprostinil 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.eng
dc.identifier.merlin.b55147355eng
dc.identifier.otherLatchamS-081805-T2260eng
dc.identifier.urihttp://hdl.handle.net/10355/4288eng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartof2005 Freely available theses (MU)eng
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Graduate School. Theses and Dissertations. Theses. 2005 Theseseng
dc.subject.meshVentricular Pressure -- drug effectseng
dc.subject.meshHypertension, Pulmonary -- drug therapyeng
dc.subject.meshEpoprostenol -- analogs & derivativeseng
dc.subject.meshHypertrophy, Right Ventricular -- etiologyeng
dc.subject.meshModels, Animaleng
dc.titleEffects of treprostinil sodium in a monocrotaline-induced rat model of pulmonary hypertensioneng
dc.typeThesiseng
thesis.degree.disciplineMicrobiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelMasterseng
thesis.degree.nameM.S.eng


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