The cardiovascular actions of omapatrilat in spontaneously hypertensive rats

Omapatrilat is a newly developed vasopeptidase inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase and has potent antihypertensive efficacy. However, the specific effect of omapatrilat on cardiac function and left ventricular hypertrophy with hypertension remains controversial. Therefore, we investigated the effect of omapatrilat on blood pressure, cardiac hypertrophy, and cardiac function in spontaneously hypertensive rats (SHR). Studies were performed in SHR that received vehicle (n = 9), omapatrilat (n = 10), or fosinopril (ACE inhibitor, n = 7) by daily gavage for 56 days. Systolic blood pressure (SBP) and mean blood pressure (MBP) were measured by tail plethysmography. Left ventricular fractional shortening and left ventricular mass were measured by echocardiography at day 56. Omapatrilat and fosinopril significantly decreased SBP and MBP from day 1 through day 56, and omapatrilat markedly reduced SBP and MBP compared with fosinopril from day 21 to day 56. Although both omapatrilat and fosinopril decreased left ventricular mass and left ventricular mass-to-body weight ratio with increased LV fractional shortening, omapatrilat had a more potent effect on the reduction of left ventricular mass and improvement of cardiac function. This study shows that in SHR, omapatrilat mediated a potent and stable antihypertensive effect and a reduction in left ventricular mass with improvement of cardiac function, compared with ACE inhibition alone.