Related Experiment Videos
Endothelin-receptor gene-expression in rat endotoxemia
1Department of Anesthesiology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. michael.bucher@klinik.uni-regensburg.de
Intensive Care Medicine
|May 25, 2002
Summary
Sepsis downregulates endothelin-A (ET(A)) receptors in the lung, potentially mediated by tumor necrosis factor alpha. This receptor downregulation may explain the reduced vascular response to endothelin-1 in pulmonary circulation during severe sepsis.
Area of Science:
- Cardiovascular Physiology
- Sepsis Pathophysiology
- Molecular Biology
Background:
- Severe sepsis is associated with a reduced vascular response to endothelin-1.
- The regulation of endothelin-receptor subtypes ET(A) and ET(B) is of interest in this context.
Purpose of the Study:
- To investigate the regulation of ET(A) and ET(B) receptor gene expression during severe sepsis.
- To determine the role of tumor necrosis factor alpha in this regulation.
Main Methods:
- Prospective animal study using lipopolysaccharide-induced endotoxemia in rats.
- Cell culture study with aortic vascular smooth muscle cells.
- Analysis of ET(A)/ET(B) receptor gene expression and tumor necrosis factor alpha levels.
Main Results:
- ET(A)/ET(B) receptor gene expression was significantly downregulated in the lung but not the kidney during endotoxemia.
- Tumor necrosis factor alpha downregulated ET(A) receptor gene expression in vascular smooth muscle cells.
- A correlation was observed between tissue tumor necrosis factor alpha concentration and ET(A) receptor gene expression in vivo.
Conclusions:
- Sepsis downregulates ET(A) receptors at the gene expression level.
- Tumor necrosis factor alpha may mediate this downregulation.
- Downregulation of ET(A) receptors could contribute to the attenuated vascular response to endothelin-1 in the pulmonary circulation.