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.
