Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy

Abstract

Aims. Although ACE inhibitors slow progression of diabetic renal disease, the mortality and morbidity is still high. As other hormonal factors are involved, inhibition of vasopeptidases could further reduce progression. We studied dual inhibition of angiotensin converting enzyme and neutral endopeptidase in a model of progressive diabetic renal injury. The major endpoints were reductions in systemic blood pressure, albuminuria and renal structural injury. Methods. Diabetic spontaneously hypertensive rats were treated with the ACE inhibitor perindopril (mg·kg-1·day-1) or the vasopeptidase inhibitor omapatrilat at doses of 10 (oma10) and 40 (oma40) mg·kg-1·day-1 for 32 weeks. In vivo ACE and N..