Renoprotective Effects of Omapatrilat Are Mediated Partially by Bradykinin

Abstract

Aim: To investigate the effects of omapatrilat on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathological changes as well as the participation of the bradykinin B2 receptor in WKY, SHR, and L-NAME/SHR rats. Methods: Eight groups of 17-week-old rats were examined using renal micropuncture techniques and histopathological analyses after 3 weeks of treatment: group 1, WKY control; group 2, WKY+omapatrilat (40 mg/kg/day); group 3, SHR control; group 4, SHR+omapatrilat; group 5, SHR+ L-NAME (50 mg/l); group 6, SHR+ L-NAME+omapatrilat; group 7, SHR+ L-NAME for 3 weeks followed by omapatrilat for a subsequent 3 weeks, and group 8, SHR+ L-NAME+omapatrilat+bradykinin antagonist icatibant (500 µg/kg/day). Results: In WKY and SHR, omapatrilat significantly reduced the mean arterial pressure, increased effective renal blood flow and single nephron plasma flow associated with reduced glomerular arteriolar resistances. Furthermore, omapatrilat prevented and reversed L-NAME induced urinary protein excretion, glomerular and arteriolar injuries, glomerular morphometric alterations, and glomerular apoptosis (at least, p < 0.05). Icatibant partially inhibited these beneficial effects of omapatrilat. Conclusion: Omapatrilat provided potent antihypertensive and renoprotective actions, which were mediated, in part, by bradykinin.