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Altered expression of contractile endothelin receptors in the vascular bed

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Author

  • Mikael Adner

Summary, in English

This thesis aims at characterizing the endothelin (ET) receptors in different vascular beds of man and rat. The ET-A receptor was shown to be the only contractile ET receptor present in all vascular regions, with the exception of the rat mesenteric vein where a weak ET-B receptor-mediated contraction was seen. Treatment with antisense oligodeoxynucleotides to the ET-A receptor mRNA during organ culture showed a decrease of the ET-1-induced contraction in the human temporal artery. However, in human omental arteries there was an increase in response to ET-B receptor agonists together with an increase of ET-B receptor mRNA following organ culture. This phenomenon suggests that contraction is due to upregulation of ET-B receptors. The level of expression of contractile ET-B receptors varies among different vascular regions following organ culture; it is most enhanced in small arteries and veins, whereas it is low or absent in large arteries. The upregulation seems to be most pronounced in the mesenteric region. The culture medium components do not induce upregulation of ET-B receptors, since there was no difference between addition of foetal calf serum or buffer solution. However, when the physiological conditions were altered, by the exclusion of energy supply (glucose) or during culture below normal temperature (at 4 °C), the upregulation was attenuated or totally blunted. This indicates that the phenomenon is a metabolically active process. Experiments with and without endothelium or tension did not alter the level of ET-B receptor expression. This suggests that there is no intrinsic mechanisms that keeps the ET-B receptors at low expression levels. ET-B receptors are shown to be upregulated in several vascular diseases. The use of organ culture can be a very useful tool to study both the function and the regulation of contractile ET-B receptors.

Department/s

  • Clinical and Experimental Allergy Research

Publishing year

1998

Language

English

Document type

Dissertation

Publisher

Department of Cell and Organism Biology, Lund University

Topic

  • Other Clinical Medicine

Keywords

  • Cardiovascular system
  • upregulation
  • transcriptional regulation
  • smooth muscle cells
  • plasticity
  • organ culture
  • Endothelin
  • receptor
  • Kardiovaskulära systemet

Status

Published

Research group

  • Clinical and Experimental Allergy Research

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-2890-8
  • ISRN: LUMEDW/MEMA--1049--SE

Defence date

27 March 1998

Defence time

10:15

Defence place

Lund University Hospital, Lecture room 2

Opponent

  • Pramod R. Saxena (Professor)