RENOPROTECTIVE EFFECTS OF DUAL BLOCKADE OF RENIN-ANGIOTENSIN SYSTEM WITH CANDESARTAN AND PERINDOPRIL IN STREPTOZOTOCIN INDUCED DIABETIC NEPHROPATHY
Journal
Македонски медицински преглед = Macedonian medical review
Date Issued
2013
Author(s)
Abstract
Introduction. Renin-angiotensin system (RAS) inhibition
exerts a renoprotective effect independent of blood pressure
reduction. Several studies suggest that combination
therapy with angiotensin converting enzyme inhibitor (ACEI)
and angiotensin receptor blockers (ARBs) provides a
greater antiproteinuric effect than monotherapy, perhaps
because of more prolonged and complete RAS inhibition.
The aim of the present study was to determine if a combination
therapy with perindopril and candesartan at lower
doses than monotherapy would confer greater renoprotection
in streptozotocin (STZ) induced diabetic nephropathy.
Methods. Wistar rats (n=125) were used in this study.
Diabetes was induced by a single i.p. injection of STZ (60
mg/kg). The diabetic rats (n=100) were randomly assigned
to receive vehicle, ARB-Candesartan (5 mg/kg/per d), ACE-I
-Perindopril (6 mg/kg/per d), or a combination of low dose
Candesartan+Perindopril (2,5 mg/kg/per d and 3 mg/kg/
per d) respectively, from weeks 4-12. Pathological changes
of the kidney were examined with optical and transmission
electron microscope.Results. Albumin excretion rate, kidney/body weight ratio
and renal structural changes increased significantly in untreated
diabetic rats compared to normal control rats. Treatment
with candesartan, perindopril, or both decreased these
changes. Addition of the candesartan to perindopril was more
effective in reducing renal structural changes and improvement
of renal function than monotherapy with either drug.
Conclusion. Combination therapy has the additional benefit
of requiring only low doses of ACE-I and ARBs to
achieve superior renoprotective effects in this diabetic
nephropathy model, possibly due to dual inhibitory effect
on the RAS.
exerts a renoprotective effect independent of blood pressure
reduction. Several studies suggest that combination
therapy with angiotensin converting enzyme inhibitor (ACEI)
and angiotensin receptor blockers (ARBs) provides a
greater antiproteinuric effect than monotherapy, perhaps
because of more prolonged and complete RAS inhibition.
The aim of the present study was to determine if a combination
therapy with perindopril and candesartan at lower
doses than monotherapy would confer greater renoprotection
in streptozotocin (STZ) induced diabetic nephropathy.
Methods. Wistar rats (n=125) were used in this study.
Diabetes was induced by a single i.p. injection of STZ (60
mg/kg). The diabetic rats (n=100) were randomly assigned
to receive vehicle, ARB-Candesartan (5 mg/kg/per d), ACE-I
-Perindopril (6 mg/kg/per d), or a combination of low dose
Candesartan+Perindopril (2,5 mg/kg/per d and 3 mg/kg/
per d) respectively, from weeks 4-12. Pathological changes
of the kidney were examined with optical and transmission
electron microscope.Results. Albumin excretion rate, kidney/body weight ratio
and renal structural changes increased significantly in untreated
diabetic rats compared to normal control rats. Treatment
with candesartan, perindopril, or both decreased these
changes. Addition of the candesartan to perindopril was more
effective in reducing renal structural changes and improvement
of renal function than monotherapy with either drug.
Conclusion. Combination therapy has the additional benefit
of requiring only low doses of ACE-I and ARBs to
achieve superior renoprotective effects in this diabetic
nephropathy model, possibly due to dual inhibitory effect
on the RAS.
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