Effects of the combination of an angiotensin II antagonist with an HMG-CoA reductase inhibitor in experimental diabetes
Open accessAbstract
Background Angiotensin II type 1 (AT1) receptor antagonists and 3-hydroxy-3-methylglutaryl conenzyme A (HMG-CoA) reductase inhibitors have been shown to confer renoprotection. However, the renal effects of the combination of an AT1 receptor antagonist and an HMG-CoA reductase inhibitor in experimental diabetes are unknown.Methods Diabetes was induced by injection of streptozotocin in Wistar rats. Diabetic rats were randomly treated with losartan, an AT1 receptor antagonist, or simvastatin, an HMG-CoA reductase inhibitor, as well as the combination of both for eight weeks. Albumin excretion rate (AER) and plasma concentrations of blood urea nitrogen (BUN), creatinine, cholesterol, and triglycerides were measured. Renal injury was evaluated. Immunohistochemical staining of transforming growth factor beta1 (TGF beta 1) and vascular endothelial growth factor (VEGF) were performed.Results Increased AER in diabetic rats was attenuated by treatment with either losartan or simvastatin and further reduced by the combination of the two. Elevated plasma concentrations of BUN and creatinine were only reduced by the combination. There was no significant difference in plasma concentrations of cholesterol and triglycerides between control and diabetic rats and neither was influenced by losartan or simvastatin. Kidney pathologic injury was attenuated by losartan, but not simvastatin, compared to diabetic animals. Overexpression of TGF beta 1 and VEGF was observed in the glomeruli of diabetic rats and was attenuated by losartan, simvastatin, or the combination of both to a similar level.Conclusion The combination of an angiotensin antagonist with an HMG-CoA reductase inhibitor confers superiority over monotherapies on renal function, as assessed by prevention of albuminuria and rise in plasma BUN and creatinine. However, no advantage of combination therapy was seen with respect to attenuating renal structural injury and renal expression of TGF beta and VEGF in experimental diabetes.
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Emerging evidence indicates that adding a statin to angiotensin II system inhibition or AT-1 receptor blockade yields greater improvements in endothelial dysfunction, inflammation, and oxidative stress.
“On the other hand, evidence for the possibility of obtaining a more marked effect on endothelial dysfunction, inflammation, and oxidative stress by combining statins with the inhibition of angiotensin II system or blocking AT-1 recep- tors is emerging.[41][42][43][44]”
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- Authors
- Qin, J., Zhang, Z., Liu, J., Sun, L., Hu, L., Cooper, M. E., & Cao, Z.
- Affiliations
- Shanxi Provincial People’s Hospital (CN)
- Shanxi Medical University (CN)
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Cao, Zemin
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 64
- Issue
- 2
- Pages
- 565-571
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2049998205
- Cited by
- 42
- References
- 32
- Citations by year
- 2019: 1 · 2017: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Juvenile Diabetes Research Foundation International
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- angiotensin receptor blockers, statins, losartan, simvastatin, combination therapy, diabetic nephropathy, albuminuria, renal protection, TGF-β1, vascular endothelial growth factor, streptozotocin-induced diabetes, glomerular injury, hypercholesterolemia
- MeSH terms
- Albuminuria, Animals, Antihypertensive Agents, Blood Urea Nitrogen, Creatinine, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Drug Therapy, Combination, Female, Kidney, Male, Transforming Growth Factor beta, Rats, Wistar, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Losartan, Simvastatin, Vascular Endothelial Growth Factor A, Angiotensin II Type 1 Receptor Blockers, Rats, Transforming Growth Factor beta1
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