Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

Abstract

BACKGROUND:

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats.

METHODS:

ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol.

RESULTS:

ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats.

CONCLUSIONS:

Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action.

• Authors: Md Abdul Hye Khan, Jan Neckář, Jasmine Haines, John D Imig
• Journal: American journal of hypertension (Am J Hypertens) Vol. 27 Issue 8 Pg. 1087-95 (Aug 2014) ISSN: 1941-7225 [Electronic] United States
• PMID: 24598210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Blood Glucose
• Oxadiazoles
• azilsartan

Topics

• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Animals
• Benzimidazoles (therapeutic use)
• Blood Glucose (metabolism)
• Blood Pressure (drug effects)
• Diabetic Nephropathies (pathology, prevention & control)
• Endothelium, Vascular (drug effects)
• Glucose Intolerance (prevention & control)
• Glucose Tolerance Test
• Hyperglycemia (drug therapy)
• Male
• Oxadiazoles (therapeutic use)
• Oxidative Stress (drug effects)
• Rats
• Rats, Zucker