Nephrol Dial Transplant (2003) 18: 2005-2013
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Beneficial and adverse renal and vascular effects of the vasopeptidase inhibitor omapatrilat in renovascular hypertensive rats
1Department of Medicine, Division of Nephrology and 2Department of Pathology, University Hospital Hamburg-Eppendorf and 3Department of Pathology, University Hospital Erlangen, Germany
Correspondence and offprint requests to: Ulrich O. Wenzel, MD, University Hospital of Hamburg-Eppendorf, Department of Medicine, Division of Nephrology, Pav. 61, Martinistrasse 52, D-20246 Hamburg, Germany. Email: wenzel{at}uke.uni-hamburg.de
Background. Vasopeptidase inhibitors are a new class of compounds that inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase. This study determined whether treatment with the vasopeptidase inhibitor omapatrilat (OMA) produced different effects on renal and cardiovascular structure compared with inhibition of ACE by enalapril (ENP) in rats with two-kidney, one clip hypertension (2K1C).
Methods. Hypertensive 2K1C rats were randomized into four groups and studied for another 8 weeks: no treatment, OMA, ENP or ENP combined with the diuretic hydrochlorothiazide (ENP + HCTZ). Albuminuria, vascular and renal histology as well as glomerular expression of transforming growth factor-ß (TGF-ß) were determined at the end of the experiment.
Results. OMA decreased blood pressure slightly better than ENP. However, combination of ENP with a diuretic lowered blood pressure equally effective as OMA. OMA was numerically more efficient in reducing cardiovascular and renal hypertensive changes compared with ENP. In contrast, the combination of ENP + HCTZ was as efficient as OMA. However, OMA lowered overexpression of TGF-ß in the non-clipped kidney better than ENP or ENP +HCTZ. Antihypertensive therapy surprisingly decreased renal function as shown by increased plasma creatinine and urea and decreased creatinine clearance.
Conclusion. OMA is marginally more potent compared with ENP alone in lowering blood pressure and preventing cardiovascular and renal injury. This effect may be due to slightly better blood pressure reduction because addition of HCTZ enhances the cardio- and nephroprotective capacity of ENP. In contrast, OMA reduces TGF-ß overexpression in the non-clipped kidney better than ENP or ENP + HCTZ. Therefore, vasopeptidase inhibition is not superior to ACE inhibition in the prevention of cardiovascular and renal damage Goldblatt hypertension.
Keywords: ACE inhibitor; enalapril; glomerulosclerosis; omapatrilat; renovascular hypertension; vasopeptidase inhibition
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