Irbesartan improves endothelial dysfunction, abnormal lipid profile, proteinuria and liver dysfunction in Zucker diabetic fatty rats independent of glucose and insulin levels

Shimamura,Munehisa; Nakagami,Hironori; Shimosato,Takashi; Moritani,Toshinori; Nakagami,Futoshi; Kiomy Osako,Mariana; Miyake,Takashi; Koriyama,Hiroshi; Shimizu,Hideo; Morishita,Ryuichi

doi:10.3892/etm.2011.307

September-October 2011 Volume 2 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September-October 2011 Volume 2 Issue 5

Full Size Image

Article

Irbesartan improves endothelial dysfunction, abnormal lipid profile, proteinuria and liver dysfunction in Zucker diabetic fatty rats independent of glucose and insulin levels

Authors:
- Munehisa Shimamura
- Hironori Nakagami
- Takashi Shimosato
- Toshinori Moritani
- Futoshi Nakagami
- Mariana Kiomy Osako
- Takashi Miyake
- Hiroshi Koriyama
- Hideo Shimizu
- Ryuichi Morishita
View Affiliations / Copyright

Affiliations: Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Kanazawa, Japan, Research Department, Nissei Bilis Co., Ltd., Ohtsu, Japan, Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan, Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Pages: 957-961
|
Published online on: June 30, 2011

https://doi.org/10.3892/etm.2011.307
Expand metrics +

Abstract

Treatment with angiotensin type 1 receptor blockers (ARBs) is known to improve renal dysfunction and glucose metabolism in obese diabetic animal models and humans. This study examined the effects of irbesartan, a unique ARB with PPARγ activation, on endothelial dysfunction, renal dysfunction, abnormal lipid profile, and liver dysfunction in obese fa/fa Zucker diabetic fatty (ZDF) rats. ZDF rats were administered irbesartan (30 mg/kg/day p.o.) for 12 weeks. Blood pressure, glucose metabolism, lipid profile and renal function were measured every 4 weeks. Response of mesenteric artery rings to acetylcholine was also evaluated as an index of endothelial function after 12 weeks of treatment. Although irbesartan did not affect glucose and insulin levels in both glucose and insulin tolerance tests, decreases in systolic blood pressure, dyslipidemia, and urinary protein excretion were noted from 4 weeks after the start of treatment and continued until 12 weeks. Endothelial and liver dysfunctions were also improved after 12 weeks of treatment. Compared to previous reports showing the effects of irbesartan at later time points such as 6 or 12 months, the present study demonstrated that a low-dose of irbesartan had favorable effects from the early period of treatment, independent of glucose metabolism. Our findings suggest that a low-dose of irbesartan improves diabetic complications quickly after starting treatment, and may support the use of irbesartan for preventing progression of diabetic complications.

View Figures

View References

1.	Persson F, Rossing P, Hovind P, et al: Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2 diabetes and microalbuminuria: an IRMA 2 substudy. Diabetes. 55:3550–3555. 2006. View Article : Google Scholar : PubMed/NCBI
2.	Ceriello A, Assaloni R, Da Ros R, et al: Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation. 111:2518–2524. 2005. View Article : Google Scholar
3.	Fliser D, Buchholz K and Haller H: Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation. 110:1103–1107. 2004. View Article : Google Scholar : PubMed/NCBI
4.	Chen FL, Yang ZH, Liu Y, et al: Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway. Endocrine. 33:331–337. 2008. View Article : Google Scholar : PubMed/NCBI
5.	Ni W, Kitamoto S, Ishibashi M, et al: Monocyte chemoattractant protein-1 is an essential inflammatory mediator in angiotensin II-induced progression of established atherosclerosis in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol. 24:534–539. 2004. View Article : Google Scholar
6.	Schupp M, Janke J, Clasen R, Unger T and Kintscher U: Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation. 109:2054–2057. 2004. View Article : Google Scholar : PubMed/NCBI
7.	Lewis EJ, Hunsicker LG, Clarke WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 345:851–860. 2001. View Article : Google Scholar
8.	Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S and Arner P: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 345:870–878. 2001. View Article : Google Scholar
9.	Lincoff AM, Wolski K, Nicholls SJ and Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 298:1180–1188. 2007. View Article : Google Scholar : PubMed/NCBI
10.	Janiak P, Bidouard JP, Cadrouvele C, et al: Long-term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats. Eur J Pharmacol. 534:271–279. 2006. View Article : Google Scholar : PubMed/NCBI
11.	Clasen R, Schupp M, Foryst-Ludwig A, et al: PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension. 46:137–143. 2005. View Article : Google Scholar : PubMed/NCBI
12.	Toblli JE, Munoz MC, Cao G, Mella J, Pereyra L and Mastai R: ACE inhibition and AT1 receptor blockade prevent fatty liver and fibrosis in obese Zucker rats. Obesity (Silver Spring). 16:770–776. 2008. View Article : Google Scholar : PubMed/NCBI
13.	Adams LA and Feldstein AE: Nonalcoholic steatohepatitis: risk factors and diagnosis. Expert Rev Gastroenterol Hepatol. 4:623–635. 2010. View Article : Google Scholar : PubMed/NCBI
14.	Munoz MC, Argentino DP, Dominici FP, Turyn D and Toblli JE: Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats. J Hypertens. 24:1607–1617. 2006. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Irbesartan improves endothelial dysfunction, abnormal lipid profile, proteinuria and liver dysfunction in Zucker diabetic fatty rats independent of glucose and insulin levels

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles