Omapatrilat, a vasopeptidase inhibitor, inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) with similar potency. The aim of this study was to investigate whether omapatrilat prevents or reverses cardiovascular remodelling and hypertension in deoxycorticosterone acetate (DOCA)-salt rats. Male Wistar rats (313±2 g, n=114) were uninephrectomized (UNX) with or without further treatment with DOCA and 1% NaCl in the drinking water. Compared with UNX control rats,

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... lt rats developed hypertension, cardiovascular hypertrophy, perivascular and interstitial cardiac fibrosis and inflammation, endothelial dysfunction and prolongation of ventricular action potential duration within 4 weeks. Administration of omapatrilat (40 mg/kg/day po) for two weeks commencing two weeks after surgery attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis and ventricular action potential prolongation. In contrast, omapatrilat treatment did not lower systolic blood pressure nor improve endothelial dysfunction. We conclude that the renin-angiotensin-aldosterone, natriuretic peptide and bradykinin systems are directly involved in the pathogenesis of cardiovascular remodelling in the DOCA-salt model of hypertension in rats, which may be independent of their effects on blood pressure.