ET_B receptor dependent alteration in aortic responses to ET-1 in the cardiomyopathic hamster

Authors: Al-Khoury, Johny; Bkaily, Ghassan; Chahine, Mirna; Jacques, Danielle; D'Orléans-Juste, Pedro

Source: Canadian Journal of Physiology and Pharmacology, Volume 84, Number 7, July 2006 , pp. 787-794(8)

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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 - 10⁻⁵mol/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 × 10⁻⁹mol/L and 1.8 × 10⁻⁹mol/L, respectively). However, in cardiomyopathic hamsters, the EC₅₀ of ET-1 in intact aortas was higher (1.5 × 10⁻⁸mol/L) than that of the endothelium denuded preparations (2.7 × 10⁻⁹mol/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 × 10⁻⁸mol/L) than that of normal hamsters (2.2 × 10⁻⁹mol/L). Pre-treatment with the ET_A receptor antagonist ABT-627 (10⁻⁵mol/L) of intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters significantly prevented ET-1 (10⁻⁷mol/L) from inducing an increase in tension. Pre-treatment with the ET_B receptor antagonist A-192621 (10⁻⁵mol/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 ET_B 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 ET_B receptors to relaxation, which in turn acts as a physiological depressor of ET-1 vasoconstriction. Our results suggest that an increase in the endothelium ET_B receptor density may play a role in the development of hypotension in UM-X7.1 cardiomyopathic hamsters.

La présente étude a eu pour but de vérifier si la réponse de l'aorte à l'ET-1 est modifiée chez les hamsters cardiomyopathiques, UM-X7,1. Nos résultats ont montré que l'ET-1 (10^-12-10^-5 mol/L) induit des augmentations soutenues, reliées à la dose, de la tension dans les aortes intactes et dénudées d'endothélium des hamsters normaux et cardiomyopathiques. Les valeurs de la CE₅₀ de l'ET-1 des aortes intactes et dénudées d'endothélium des hamsters normaux ont été similaires (2,2 × 10⁻⁹ mol/L et 1,8 × 10⁻⁹ mol/L respectivement). Toutefois, chez les hamsters cardiomyopathiques, la CE₅₀ de l'ET-1 dans les aortes intactes a été plus élevée (1,5 × 10⁻⁸ mol/L) que celle des préparations dénudées d'endothélium (2,7 × 10⁻⁹ mol/L). Les valeurs de la CE₅₀ de l'ET-1 des aortes normales et dénudées des hamsters cardiomyopathiques ont été similaires. Toutefois, la CE₅₀ de l'ET-1 dans les aortes intactes des hamsters cardiomyopathiques a été plus élevée (1,5 × 10⁻⁸ mol/L) que celle des hamsters normaux (2,2 × 10⁻⁹ mol/L). Le prétraitement des aortes intactes et dénudées d'endothélium des hamsters normaux et cardiomyopathiques au moyen de l'antagoniste des récepteurs ET_A, ABT-627 (10⁻⁵ mol/L), a prévenu de manière significative l'induction d'une augmentation de tension par l'ET-1 (10⁻⁷ mol/L). Un prétraitement avec l'antagoniste des récepteurs ET_B, A-192621 (10⁻⁵ mol/L), n'a pas eu d'effet sur l'augmentation de tension induite par l'ET-1 dans les aortes dénudées d'endothélium des hamsters normaux et cardiomyopathiques ainsi que dans les préparations intactes des animaux normaux.

Document Type: Research article

Publication date: 2006-07-01

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