Fachbereich Veterinärmedizin



    Charakterisierung eines transgenen Rattenmodells mit Koexpression des humanen Endothelin-B-Rezeptors im glatten Gefäßmuskel (2014)

    Funck, Merlind (WE 14)
    Berlin: Mensch und Buch Verlag, 2014 — IV, 99 Seiten
    ISBN: 978-3-86387-436-0
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000096228
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221

    Abstract / Zusammenfassung

    The aim of this dissertation was to analyze the pathopysiological role of the human ETBR in relation to blood pressure and blood vessel wall structure in a rat model.
    In order to achieve this, an already established transgenic rat model of the human ETBR receptor under the con-trol of a VSMC specific promoter (derived from the murine SM22α gene) was used. Two transgenic rat lines (4230 and 6707) from this model were further analyzed. Previous experi-ments showed an expression of the transgenic ETBR in various organs and isolated blood ves-sels for both lines.
    Blood pressure was measured using radio telemetry over a period of one month to establish whether or not the co-expression of ETB could have a possible effect on the blood pressure. At the commencement of the measurements, the rats were 14 weeks of age.
    When comparing the baseline blood pressure parameters (systolic, mean, diastolic blood pres-sure) and heart rates of the transgenic rats and their non-transgenic littermates, no statistical significant differences were found.
    The treatment with the NO synthase inhibitor L-NAME, prevented the vasodilation effect of NO. This resulted in an elevated blood pressure as well as a decreased heart rate. There were, however, no statistically significant differences between the transgenic and the non-transgenic animals. All parameters normalized to similar values once L-NAME was no longer administered. In order to identify the structural phenotypes, the thoracic aorta of each of the telemetry probed animals was analyzed using histomorphometry.
    This should have confirmed a possible variation of the media induced by the co-expression of the human ETBR. Upon removal of the vessels, all animals were 18 weeks old. The histologi-cal cross-sections were digitally analyzed and the media-to-lumen ratio was measured by a specific computer program. The analysis resulted in a small but statistically significant reduc-tion in the media-to-lumen ratio in the transgenic animals of L4230 in comparison to the non-transgenic controls. In contrast, the media-to-lumen ratio of the transgenic rats of L6707 was statistically significantly higher by trend in comparison to their non-transgenic controls. From the results, it can be concluded that the co-expression of the human ETBR in the transgenic rat model has no relevant blood-pressure related effects. The structural effect was very low und not consistent.
    The model’s validity is limited by the downregulation of the transgenic expres-sion with increasing age of the animals as well as the low level of expression of the transgenic receptor.