Bosentan, a dual EDN1A/B receptor antagonist, preserved aortic and carotid endothelial function in Tg2576 mice, which overexpress APP 15, and EDN1A receptor antagonists have been shown to have therapeutic benefit in several peripheral diseases associated with abnormal activation of the endothelin system: pulmonary hypertension, some forms of renal disease, systemic arterial hypertension, heart failure, allograft rejection and diabetes/insulin resistance (reviewed in 44). This evidence concerns the gene APP and heart failure.