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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Agonist-dependent modulation of arterial endothelinA receptor function
M G Compeer1, M J P M T Meens, T M Hackeng
1Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
British Journal of Pharmacology
|February 14, 2012
Summary
Endothelin ET(A) receptors show allosteric modulation by agonists and antagonists, impacting vasoconstriction. This finding suggests new therapeutic strategies for endothelin-related diseases.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Molecular Biology
Background:
- Endothelin-1 (ET-1) induces prolonged vasoconstriction, poorly reversed by ET(A) receptor antagonists.
- The hypothesis explored allosteric modulation of ET(A) receptors by various ligands.
Purpose of the Study:
- To investigate the allosteric modulation of endothelin ET(A) receptors.
- To understand the influence of endogenous agonists and exogenous ligands on ET(A) receptor function.
Main Methods:
- Isolated rat mesenteric resistance arteries were used.
- Experiments were conducted in wire myographs with L-NAME and indomethacin.
- Responses to endothelins and receptor antagonists (BQ123, PD156707) were analyzed.
Main Results:
- Endothelins caused contractions with varying potency (ET-1 = ET-2 > ET-3).
- ET(A) antagonists (BQ123, PD156707) reduced sensitivity and relaxed contractile responses.
- Antagonist effects were agonist-dependent and showed discrepancies between prevention and inhibition.
Conclusions:
- Arterial smooth muscle ET(A) receptor function is allosterically modulated by agonists and antagonists.
- This modulation has implications for diagnosing and treating endothelin-related diseases.
- Agonist-dependent allosteric modulation offers potential for targeted pharmacotherapy.
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