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Title: Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats.
Austin Authors: Cao, Zemin;Bonnet, Fabrice;Davis, B;Allen, Terri J;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
Issue Date: 1-Jun-2001
Publication information: Clinical Science 2001; 100(6): 591-9
Abstract: Angiotensin II plays a pivotal role in the development of diabetic nephropathy, but it remains controversial as to the best approach to effectively block the actions of this hormone in the kidney. The aim of the present study was to explore the effects of long-term treatment (8 months) with a combination of an angiotensin type 1 (AT1) receptor antagonist, irbesartan (15 mg/kg per day), and an angiotensin-converting enzyme (ACE) inhibitor, captopril (100 mg/kg per day), in diabetic spontaneously hypertensive rats. Captopril treatment reduced blood pressure (163+/-3 mmHg versus diabetic 201+/-3 mmHg), but not albumin excretion rate (43.8x//1.3 mg/day versus diabetic 46.8x//1.4 mg/day). Irbesartan treatment was associated with a similar reduction in blood pressure (173+/-3 mmHg) to captopril, and albumin excretion rate was reduced (14x//1.5 mg/day). The combination of irbesartan and captopril induced further reductions in blood pressure (140+/-3 mmHg) and albumin excretion rates (4.0x//1.5 mg/day). Gene expression of transforming growth factor beta-1 was reduced by all treatments to a similar level as assessed by in situ hybridization. These results demonstrate the additive hypotensive and anti-albuminuric effects of an ACE inhibitor and an AT1 receptor, suggesting that combination therapy is an approach not only more effective at reducing blood pressure, but also at retarding the development of diabetic nephropathy.
Gov't Doc #: 11352773
Journal: Clinical Science
Type: Journal Article
Subjects: Albuminuria.prevention & control
Angiotensin II.metabolism
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Antihypertensive Agents.therapeutic use
Biphenyl Compounds.therapeutic use
Blood Pressure.drug effects
Captopril.therapeutic use
Drug Therapy, Combination
Gene Expression
Hypertension.drug therapy.metabolism.pathology
RNA, Messenger.genetics
Rats, Inbred SHR
Tetrazoles.therapeutic use
Transforming Growth Factor beta.genetics.metabolism
Transforming Growth Factor beta1
Appears in Collections:Journal articles

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