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Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture.

Johnsson, Evelina; Maddahi, Aida LU ; Wackenfors, Angelica LU and Edvinsson, Lars LU (2008) In European Journal of Pharmacology 582(1-3). p.94-101
Abstract
Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and... (More)
Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries but produced significant vasoconstriction after organ culture. The endothelin ET(B) receptor mRNA level and the receptor protein immunoreactivity were increased, whereas the level of endothelin ET(A) receptor mRNA was down-regulated but not its receptor protein immunoreactivity after organ culture. Pharmacological inhibition of endothelium-derived dilatory mediators did not influence endothelin ET(A) or ET(B) receptor-mediated vasoconstriction in fresh segments. In cultured arteries, inhibition of endothelial vasodilators potentiated the effect of sarafotoxin 6c. In conclusion, endothelin ET(B) receptor stimulation in cultured coronary arteries elicits vasoconstriction. This is likely not related to endothelial dysfunction with putative loss of its vasodilator components, but rather explained by the up-regulation of contractile endothelin ET(B) receptors on smooth muscle cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
582
issue
1-3
pages
94 - 101
publisher
Elsevier
external identifiers
  • pmid:18242601
  • wos:000253877700012
  • scopus:39149117359
ISSN
1879-0712
DOI
10.1016/j.ejphar.2007.12.030
language
English
LU publication?
yes
id
8e3481c8-37a4-4923-b7f9-e147d4bc8101 (old id 1042337)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18242601?dopt=Abstract
date added to LUP
2008-03-06 11:26:27
date last changed
2017-01-01 07:41:28
@article{8e3481c8-37a4-4923-b7f9-e147d4bc8101,
  abstract     = {Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries but produced significant vasoconstriction after organ culture. The endothelin ET(B) receptor mRNA level and the receptor protein immunoreactivity were increased, whereas the level of endothelin ET(A) receptor mRNA was down-regulated but not its receptor protein immunoreactivity after organ culture. Pharmacological inhibition of endothelium-derived dilatory mediators did not influence endothelin ET(A) or ET(B) receptor-mediated vasoconstriction in fresh segments. In cultured arteries, inhibition of endothelial vasodilators potentiated the effect of sarafotoxin 6c. In conclusion, endothelin ET(B) receptor stimulation in cultured coronary arteries elicits vasoconstriction. This is likely not related to endothelial dysfunction with putative loss of its vasodilator components, but rather explained by the up-regulation of contractile endothelin ET(B) receptors on smooth muscle cells.},
  author       = {Johnsson, Evelina and Maddahi, Aida and Wackenfors, Angelica and Edvinsson, Lars},
  issn         = {1879-0712},
  language     = {eng},
  number       = {1-3},
  pages        = {94--101},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2007.12.030},
  volume       = {582},
  year         = {2008},
}