Key result
ET-1 increases LV dp/dtmax by ~16% in dogs with CHF, suggesting a functional receptor shift.
There is a functional shift in endothelin receptor subtypes in heart failure, with attenuated ETB-mediated responses and more prominent ETA-mediated responses.
Supports functional ET receptor shift in experimental CHF; leaves open clinical relevance of ETA predominance.
To clarify the functional role of endothelin-A/endothelin- B (ETA/ETB) receptors in congestive heart failure (CHF), we examined the effects of a non-selective endothelin receptor agonist, endothelin-1 (ET-1), and a selective ETB receptor agonist, sarafotoxin S6c. CHF was induced in dogs by rapid ventricular pacing and resulted in decreased left ventricular dp/dtmax, decreased cardiac output and increased pulmonary vascular resistance. Sarafotoxin S6c (0.3 nmol/kg) resulted in decreased left ventricular dp/dtmax (-26 +/- 2%), decreased cardiac output (-47 +/- 3%) and increased pulmonary vascular resistance (+48 +/- 10%) in dogs without CHF. The effects of sarafotoxin S6c were attenuated in dogs with CHF (-12 +/- 5% in left ventricular dp/dtmax, -19 +/- 5% in cardiac output and +7 +/- 5% in pulmonary vascular resistance). In contrast, ET-1 (0.5 nmol/kg) had no effect on left ventricular dp/dtmax in dogs without CHF and increased left ventricular dp/dtmax by 16 +/- 3% in dogs with CHF. These data indicate that reduced cardiac contractile and pulmonary vasoconstrictor responses via the ETB receptor are attenuated and that responses mediated by the ETA receptor are more prominent in the context of CHF. This suggests a functional shift of endothelin receptor subtypes in CHF.
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Tadano et al. (2004) studied Congestive heart failure. Endothelin-1 (ET-1) and Sarafotoxin S6c vs. Dogs without congestive heart failure was evaluated on Left ventricular dp/dtmax, cardiac output, and pulmonary vascular resistance. In dogs with CHF, responses to the ETB agonist sarafotoxin S6c were attenuated, while the ETA agonist ET-1 increased left ventricular dp/dtmax by 16 +/- 3%, suggesting a functional receptor shift.
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