Despite the potential therapeutic benefits of increased natriuretic peptide and bradykinin levels, neprilysin inhibitor therapy has only modest efficacy in essential hypertension and heart failure, which might be due in part to the inhibition of neprilysin metabolism of the vasoconstrictors angiotensin II and endothelin 1, and the increased plasma angiotensin II, endothelin 1 and noradrenaline levels that accompany neprilysin inhibitor therapy (17). This evidence concerns the gene KNG1 and heart failure.