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Published on: July 3, 2013
Endothelin in the kidney in malignant phase hypertension
C E Whitworth1, M M Veniant, J D Firth
1Centre for Genome Research, University of Edinburgh, UK.
Hypertension (Dallas, Tex. : 1979)
|December 1, 1995
Summary
Increased kidney endothelin-1 mRNA in malignant hypertension does not cause the condition. Blocking endothelin receptors with bosentan did not prevent the transition to malignant hypertension in susceptible rats.
Area of Science:
- Nephrology
- Cardiovascular Research
- Molecular Biology
Background:
- Endothelin's role in malignant hypertension is suggested by increased circulating levels in animal models.
- A specific rat model with genetic predisposition to spontaneous malignant hypertension has been identified.
Purpose of the Study:
- To investigate the expression of endothelin genes (ET-1, ET-2, ET-3) in the kidneys of rats with different hypertensive states.
- To determine if endothelin-1 (ET-1) signaling is critical in the progression from benign to malignant hypertension.
Main Methods:
- Quantitative RNase protection assays were used to measure endothelin gene expression in rat kidney tissue.
- Hypertensive rats susceptible to malignant hypertension were treated with bosentan, a combined endothelin receptor antagonist.
- Gene expression levels were compared across groups: malignant hypertension, benign hypertension (with/without susceptibility), and normotensive controls.
Main Results:
- Endothelin-1 mRNA levels were significantly elevated in rats with malignant hypertension compared to other groups.
- Treatment with bosentan did not result in hypotensive effects or alter the incidence of malignant hypertension.
- No significant difference in the development of malignant hypertension was observed between bosentan-treated and control groups.
Conclusions:
- Elevated renal endothelin-1 mRNA expression in this malignant hypertension model may be a consequence of cellular damage or ischemia, not a cause.
- Blockade of endothelin-1-mediated effects does not prevent the transition from benign to malignant hypertension in this susceptible rat model.
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