Abstract
The contribution of angiotensin-(1–7) [Ang-(1–7)] to the antihypertensive actions of omapatrilat (OMA), a novel vasopeptidase inhibitor, was evaluated in 15 salt-sensitive, low renin, hypertensive subjects as a sub-study of a multi-center randomized, double-blind, parallel study of 4 wks duration. As illustrated in the Figure, OMA (40 mg) caused statistically significant rises in the urinary excretion of both Ang-(1–7) (upper panel) and atrial natriuretic peptide (ANP, middle panel) throughout the dosing period at day 28 of treatment (-After). The effects of OMA on Ang-(1–7) and ANP excretion were associated with a sustained control of blood pressure as denoted by the differences in the 24 hr ambulatory systolic blood pressure measurements at days 0 (SBP, before) and 28 of treatment (SBP, After).
A single molecule inhibiting neutral endopeptidase and angiotensin converting enzyme effectively controlled salt-sensitive hypertension by a mechanism related to inhibition of NEP 24.11 for which Ang-(1–7) is a substrate. These data are the first to show a role of Ang-(1–7) to the antihypertensive renal response of a novel vasopeptidase inhibitor in the treatment of essential hypertension.
