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    Die Bedeutung von Endothelien und dem Endothelinrezeptorsystem für die Pathogenese der Myokardhypertrophie und Nephrosklerose bei Ratten mit renovaskulärem Hypertonus (2K1C-Modell nach Goldblatt) (2000)

    Art
    Hochschulschrift
    Autor
    George, Ines
    Quelle
    Berlin, 2000 — 90 Seiten
    Kontakt
    Institut für Tierschutz und Tierverhalten

    Königsweg 67
    Gebäude 21, 1. OG
    14163 Berlin
    Tel.: +49 30 838 62901 (Sekretariat)
    email: tierschutz@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    In this thesis, hypertonic rats were produced using the Goldblatt method and were treated with selective and combined endothelin antagonists (BQ 123, IRL 1038 and BOSENTAN).Each week blood pressures was measured using in a non-surgical method, after 44 days the animals were killed and their organs (heart and kidneys) were removed. These organs were examined by means of histological and screen analytical procedures.The right relative organ weight between the right kidney of the group which was sham. operated and the clipped group (MC) which was not treated was significant (p<0,01). The same can be stated comparing the relative weight of the heart in both groups. In addition, this thesis describes the significant difference, given p < 0,05, between the relative weight of the left kidney~as part of the BQ123 group and of the clipped group (2K1C) which was not treated.The operative plantation of a nephroartery stenosis leads to a renovascular hypertonus which also persists when treated with selective and combined endothelin antagonists.Heart:The perivascular fibrosis in the heart is no stronger with rats suffering from a renovascular hypertonus (2K1C) than with the group that was sham -operated. This means that endothelin antagonism -Iitye no effect on the perivascular fibrosis. There- is; however, an effect on the media/lumen ratio of the intracardial arteries. In comparison with the group that was scheinoperiert, the renovascular hypertension group which was not treated is characterized by a growing media thickness.If rats suffering from renovascular hypertension are reated with BQ123 this effect do no longer shows.The treatment with IRL1038, however, strengthens the media/lumen ratio, the mediathickness is stronger pronounced than it is with the 2K1C group that was not treated.Using IRL 1038 as a blockade the cardial fibrosis in the heart will be reduced which does not apply to the control group suffering from renovascular hypertension which was not treated.Kidney:The combination of endothelin receptor antagonists and Bosentan as well as using IRL1038 as a blockade cause an increase of the media thickness on the stenotic side.On the left stenotic kidney the control group that was not treated suffering from renovascular hypertension shows a Significant increase of interstitial fibrosis as opposed to the animals thatwere sham,operated. The group treated with BQ123 and the group treated with Bosentan show a clear increase of interstitial fibrosis as opposed to the 2KIC group that was not treated.In the right unclipped kidney the control group that was not treated suffering from renovascular hypertension shows a significant increase of interstitial fibrosis as opposed to the animals that were shamoperated.A clear reduction of interstitial fibrosis can be observed in the 2K1C group treated withIRL1038 as opposed to the control group suffering from renovascular hypertension that were not treated.This thesis proves that selective or combined endothelin antagonists have no antihypertensive effect on rats suffering from renovascular hypertension. The reduction of cardial fibrosis when treated with IRL1038 was described. Furthermore, it is shown for the first time that a endothelin receptor blockade, using BQ123, does not have any antifibriotic effect in the stenotic kidney.