Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat

Abstract

Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand 125I-MK351A and the NEP inhibitor radioligand 125I-RB104 in rats that received oral omapatrilat (40 mg·day-1·kg-1) for 3 days. In vitro autoradiography was used to examine the distribution of ACE and NEP in the kidney, aorta, heart, adrenal gland, lung, intestine, liver, spleen and brain, and to ass..