Azilsartan Improves Glycemic Status and Reduces Kidney Damage in Zucker Diabetic Fatty Rats

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 fatt...

Full description

Saved in:

Bibliographic Details
Published in:	American journal of hypertension 2014-08, Vol.27 (8), p.1087-1095
Main Authors:	Khan, Md. Abdul Hye, Neckář, Jan, Haines, Jasmine, Imig, John D.
Format:	Article
Language:	eng
Subjects:	Angiotensin II Type 1 Receptor Blockers - therapeutic use Animals Antihypertensives Benzimidazoles - therapeutic use Blood Glucose - metabolism Blood pressure Blood Pressure - drug effects Diabetes Diabetic Nephropathies - pathology Diabetic Nephropathies - prevention & control Endothelium, Vascular - drug effects Glucose Glucose Intolerance - prevention & control Glucose Tolerance Test Hyperglycemia Hyperglycemia - drug therapy Hypertension Inflammation Kidney diseases Laboratory animals Male Metabolic syndrome Oxadiazoles - therapeutic use Oxidative stress Oxidative Stress - drug effects Rats Rats, Zucker Rodents
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0895-7061 1879-1905