Dual inhibition of angiotensin converting enzyme and neutral endopeptidaseby omapatrilat in rat in vivo

The pharmacological profile of a vasopeptidase inhibitor is dependent on th e ratio of neutral endopeptidase (NEP) vs angiotensin converting enzyme (AC E) inhibition of the particular drug. We used in vitro autoradiography to d etermine the local renal and cardiac NEP and ACE inhibition after oral trea tment with the dual NEP/ACE inhibitor omapatrilat in rat. Maximal inhibitio n of both renal NEP and ACE was achieved at the omapatrilat dose of 40 mg k g(-1) day(-1). Effective local ACE inhibition was detected also in the myoc ardium. The haemodynamic effects were similar to captopril, but omapatrilat treatment produced more favorable effect on natriuretic peptide levels. In conclusion, good tissue penetration of omapatrilat and balanced NEP/ACE in hibition may prove to be useful in the treatment of hypertension and heart failure. (C) 2001 Academic Press.