Sensitivity to Endothelin-1 in Mice Lacking Nitric Oxide Synthase
Author Information
Author(s): De Gottardi Andrea, Biecker Erwin, Koshy Abraham, Bohler Dieter, Shaw Sidney, Sägesser Hans, Reichen Jürg
Primary Institution: Department of Clinical Pharmacology, University of Berne
Hypothesis
Sensitivity to endothelin is increased in mice lacking the endothelial cell NO synthase gene.
Conclusion
Livers of ecNOS knockout mice have a decreased sensitivity to endothelin at physiologic concentrations due to decreased expression of ETA receptors.
Supporting Evidence
- Endothelin increased hepatic vascular resistance in a dose-dependent manner in both strains.
- The increase in resistance was significantly less in ecNOS knockout mice at physiologic concentrations.
- Expression of heme-oxygenases and adrenomedullin was similar in both groups.
- mRNA levels of pre-pro-endothelin-1 and ETB receptor were comparable in both strains.
- mRNA for ETA receptor was decreased by 65% in ecNOS knockouts.
Takeaway
The study found that mice without a specific enzyme are less sensitive to a substance that usually constricts blood vessels in the liver.
Methodology
The response of vascular resistance to endothelin was assessed in perfused livers of ecNOS knockout and wild type mice, with RNA and protein isolation for quantitative PCR and Western blotting.
Limitations
The study did not explore the mechanisms by which ETA receptors contribute to the decreased sensitivity to endothelin.
Participant Demographics
All mice were male and of the same genetic background (C57BL/6J).
Statistical Information
P-Value
0.0005
Statistical Significance
p = 0.0005
Digital Object Identifier (DOI)
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