We developed a C-domain-selective derivative of lisinopril (lisinopril-tryptophan [lisW-S]) by substituting a tryptophan for the P2’ proline.28–30 In TtRhRen mice (LinA3), a model of Ang II–dependent hypertension, lisW-S effectively reduced Ang II levels and lowered BP without influencing BK levels.30 The effect of lisW-S combined with a NEP inhibitor could have the same beneficial effects as omapatrilat but without the undesirable properties attributed to BK accumulation. Here, MME is linked to hypertensive disorder.