ETBreceptor dependent alteration in aortic responses to ET-1 in the cardiomyopathic hamsterThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

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 EC50values of ET-1 of both intact and endothelium denuded aortas of normal hamsters were similar (2.2 × 10−9 mol/L and 1.8 × 10−9 mol/L, respectively). However, in cardiomyopathic hamsters, the EC50of ET-1 in intact aortas was higher (1.5 × 10−8 mol/L) than that of the endothelium denuded preparations (2.7 × 10−9 mol/L). The EC50of ET-1 in normal and cardiomyopathic hamster denuded aortas were similar. However, the EC50of ET-1 in intact aortas of cardiomyopathic hamster was higher (1.5 × 10−8 mol/L) than that of normal hamsters (2.2 × 10−9 mol/L). Pre-treatment with the ETAreceptor 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 ETBreceptor 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 ETBreceptors 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 ETBreceptors to relaxation, which in turn acts as a physiological depressor of ET-1 vasoconstriction. Our results suggest that an increase in the endothelium ETBreceptor density may play a role in the development of hypotension in UM-X7.1 cardiomyopathic hamsters.