EDNRA and heart failure: In contrast, bosentan appeared to increase the early risk of heart failure hospitalization because of fluid retention.374 Human clinical trials with enrasentan and ETA-selective darusentan were also unsuccessful.375,376 Interestingly, a follow-up mechanistic study showed that sympathetic neuron-specific but not cardiomyocyte-specific ETA knockout reduced cardiac remodeling induced by pressure overload.