Comparative efficacy of AHU-377, a potent neprilysin inhibitor, in two rat models of volume-dependent hypertension

Background Progressive hypertension and deteriorating renal function are hallmarks of cardio-renal syndromes. Historically, the deoxycorticosterone acetate (DOCA)-salt model has been used to assess the therapeutic potential of antihypertensives in the setting of low renin and volume-dependent hypertension. Dahl-salt-sensitive (Dahl-SS) rats represent a genetic model of volumedependent hypertension and possess similar features to the DOCA model, including higher natriuretic peptide tone. Neprilysin inhibitors (NEPi) prevent the degradation of natriuretic peptides and activate cGMP signalling pathways that regulate volume and blood pressure. Antihypertensive effects of NEPi have been demonstrated in both DOCA and Dahl-SS models; however, the relative efficacy of NEPi in these two models has not been studied directly. Here, we characterized the natriuretic peptide tone in DOCA and Dahl-SS rats and compared antihypertensive effects of a NEPi, (AHU-377).