Despite the availability of many classes of antihypertensive drugs, control of hypertension remains suboptimal in the majority of treated patients, highlighting the need for new therapeutic strategies.42,43 To address this, we investigated the BP and cardiovascular properties of a novel drug combination, C-domain–selective ACE inhibitor (lisW-S) combined with a NEP inhibitor (sacubitril), in a mouse model of Ang II–dependent hypertension, and compared the effects to those of omapatrilat, which inhibits ACE C-domain and N-domain and NEP (recapitulated by lisinopril+sacubitril in our study). This evidence concerns the gene ACE and hypertensive disorder.