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Published on: June 21, 2016
ETB receptor dependent alteration in aortic responses to ET-1 in the cardiomyopathic hamster
Johny Al-Khoury1, Ghassan Bkaily, Mirna Chahine
1Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Insights
Cardiomyopathic hamsters show a reduced aortic contraction response to endothelin-1 (ET-1). This alteration is linked to endothelial ETB receptors, potentially contributing to hypotension in these animals.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Animal Models
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor involved in cardiovascular regulation.
- UM-X7.1 hamsters serve as a model for studying cardiomyopathy and its associated vascular alterations.
Purpose of the Study:
- To investigate alterations in the aortic endothelin-1 (ET-1) response in UM-X7.1 cardiomyopathic hamsters.
- To determine the role of endothelial ETA and ETB receptors in mediating ET-1 responses in this model.
Main Methods:
- Vascular tension measurements in intact and endothelium-denuded aortic rings from normal and cardiomyopathic hamsters.
- Dose-response studies with ET-1.
- Pharmacological blockade of ETA and ETB receptors using specific antagonists (ABT-627 and A-192621).
Main Results:
- ET-1 induced dose-dependent contractions in both normal and cardiomyopathic hamster aortas.
- The EC50 for ET-1 was significantly higher in intact aortas of cardiomyopathic hamsters compared to normal hamsters, indicating an attenuated response.
- Blockade of ETA receptors inhibited ET-1 contractions, while blockade of ETB receptors potentiated ET-1 contractions in intact aortas of cardiomyopathic hamsters.
- The observed alterations in ET-1 response were dependent on the presence of the endothelium.
Conclusions:
- A diminished contraction response to ET-1 occurs in the aortas of UM-X7.1 cardiomyopathic hamsters.
- The endothelium, particularly through enhanced ETB receptor activity, plays a significant role in modulating ET-1's vasoconstrictive effects in this model.
- Increased endothelial ETB receptor density may contribute to hypotension observed in UM-X7.1 cardiomyopathic hamsters.
Abstract:
The aim of this study was to verify whether an alteration in the aortic endothelin-1 (ET-1) response takes place in UM-X7.1 cardiomyopathic hamsters. Our results showed that ET-1 (10(-12) - 10(-5) mol/L) induces dose-dependent sustained increases in tension in the intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters. The EC50 values of ET-1 of both intact and endothelium denuded aortas of normal hamsters were similar (2.2 x 10(-9) mol/L and 1.8 x 10(-9) mol/L, respectively). However, in cardiomyopathic hamsters, the EC50 of ET-1 in intact aortas was higher (1.5 x 10(-8) mol/L) than that of the endothelium denuded preparations (2.7 x 10(-9) mol/L). The EC50 of ET-1 in normal and cardiomyopathic hamster denuded aortas were similar. However, the EC50 of ET-1 in intact aortas of cardiomyopathic hamster was higher (1.5 x 10(-8) mol/L) than that of normal hamsters (2.2 x 10(-9) mol/L). Pre-treatment with the ETA receptor antagonist ABT-627 (10(-5)mol/L) of intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters significantly prevented ET-1 (10(-7) mol/L) from inducing an increase in tension. Pre-treatment with the ETB receptor antagonist A-192621 (10(-5) mol/L) had no effect on the ET-1-induced increase in tension in endothelium denuded aortas of both normal and cardiomyopathic hamsters, as well as in intact preparations of normal animals. However, blockade of the ETB receptors in intact aortas of cardiomyopathic hamsters significantly (p < 0.001) potentiated the ET-1-induced increase in tension. In summary, an attenuation of the contraction response to ET-1 was found in UM-X7.1 cardiomyopathic hamsters when compared with normal age-matched hamsters. This alteration of the ET-1 effect in the aortas of cardiomyopathic hamsters seems to be dependent on the presence of the endothelium and could be due, in part, to an increase in the contribution of endothelial ETB receptors to relaxation, which in turn acts as a physiological depressor of ET-1 vasoconstriction. Our results suggest that an increase in the endothelium ETB receptor density may play a role in the development of hypotension in UM-X7.1 cardiomyopathic hamsters.
