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Title: Vasopeptidase inhibition attenuates the progression of renal injury in subtotal nephrectomized rats.
Austin Authors: Cao, Zemin;Burrell, Louise M ;Tikkanen, Ilkka;Bonnet, Fabrice;Cooper, Mark E;Gilbert, Richard E
Affiliation: University of Melbourne Department of Medicine at Austin and Repatriation Medical Centre, Heidelberg West, Victoria, Australia
Issue Date: 1-Aug-2001
Publication information: Kidney International; 60(2): 715-21
Abstract: Vasopeptidase inhibitors are a new class of cardiovascular compounds that inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of the present study was to explore the effects of omapatrilat, a vasopeptidase inhibitor, on renal function and pathology in subtotally nephrectomized (STNx) rats.STNx rats were randomized to four groups and treated for 12 weeks: no treatment (N = 14); omapatrilat at a low dose of 10 mg/kg (L, N = 12) and at a high dose of 40 mg/kg (H, N = 10); or an ACE inhibitor, fosinopril, at a dose of 10 mg/kg (N = 12). Sham-operated rats were used as control animals (N = 12).Elevated blood pressure in STNx rats (174 +/- 9 mm Hg) was reduced by omapatrilat in a dose-dependent manner (L, 121 +/- 3 mm Hg; H, 110 +/- 3 mm Hg) and by fosinopril (149 +/- 5 mm Hg). Proteinuria in STNx rats (246 +/- 73 mg/day) was reduced by treatment with fosinopril (88 +/- 21 mg/day) and was normalized by treatment with omapatrilat (L, 30 +/- 4 mg/day; H, 20 +/- 2 mg/day vs. control 25 +/- 1 mg/day). Decreased glomerular filtration rates, elevated plasma urea and creatinine and glomerulosclerosis, and tubulointerstitial fibrosis were ameliorated by omapatrilat and fosinopril to a similar degree. Compared with fosinopril, omapatrilat treatment was associated with increased plasma renin activity and decreased renal ACE and NEP binding in a dose-dependent manner.These findings suggest that vasopeptidase inhibition may provide a useful strategy for the treatment of progressive renal disease.
Gov't Doc #: 11473654
DOI: 10.1046/j.1523-1755.2001.060002715.x
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Blood Pressure.drug effects
Disease Models, Animal
Glomerular Filtration Rate
Heart Failure.drug therapy.metabolism
Hypertension, Renal.drug therapy.metabolism.pathology
Neprilysin.analysis.antagonists & inhibitors.metabolism
Organ Size
Peptidyl-Dipeptidase A.analysis.metabolism
Proteinuria.drug therapy.pathology
Rats, Sprague-Dawley
Renal Insufficiency.drug therapy.metabolism.pathology
Appears in Collections:Journal articles

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