Effects of omapatrilat on blood pressure and renal injury in l-name and l-name plus DOCA-treated rats

Abstract

BackgroundThis study investigates the effects of chronic administration of omapatrilat (OMA) on blood pressure (BP), renal injury, and other variables in Nω-nitro-l-arginine methyl ester (L-NAME) hypertension and in the low-renin model produced by the simultaneous administration of L-NAME and deoxycorticosterone acetate (DOCA). MethodsThe control, DOCA, L-NAME, L-NAME + DOCA, L-NAME + OMA, and L-NAME + DOCA + OMA groups were used. Tail systolic BP was measured twice a week. After 4 weeks of treatment, mean arterial pressure (MAP), and metabolic, morphologic, and renal variables were measured. ResultsThe final values of MAP were 109 ± 5.1 mm Hg for the control group, 113 ± 3.0 mm Hg for DOCA, 175 ± 3.7 mm Hg for L-NAME, 193 ± 3.8 mm Hg for L-NAME + DOCA, 117 ± 3.9 mm Hg for L-NAME + OMA, and 158 ± 3.0 mm Hg for L-NAME + DOCA + OMA. The rats treated with L-NAME showed mild and scarce renal lesions, which were prevented by OMA treatment and the L-NAME + DOCA group showed proteinuria and hyaline arteriopathy, which were markedly attenuated in the L-NAME + DOCA + OMA group. Plasma urea and creatinine were significantly increased in the L-NAME + DOCA group, whereas these variables were not significantly greater in the L-NAME + DOCA + OMA group versus controls. The L-NAME + DOCA group showed relative renal and cardiac hypertrophy that was not observed in the L-NAME + DOCA + OMA group. ConclusionsThe simultaneous blockade of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) completely prevents L-NAME hypertension. Our results also show that OMA attenuates the increased BP and the renal injury in L-NAME hypertensive rats treated with DOCA. Assuming that this is a low-renin model of hypertension, the protective effect of OMA may be due to an increase in vasodilator peptides produced by both ACE and NEP inhibition.