The Effect of Chronic Candesartan Therapy on the Metabolic Profile and Renal Tissue Cytokine Levels in the Obese Zucker Rat

被引:14
作者
Ecelbarger, Carolyn M. [1 ]
Rash, Arjun [1 ]
Sinha, Rajesh K. [2 ]
Tiwari, Swasti [1 ]
机构
[1] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA
[2] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
RENIN-ANGIOTENSIN SYSTEM; II TYPE-1 RECEPTOR; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; DIABETIC-NEPHROPATHY; INDUCED INFLAMMATION; BLOOD-PRESSURE; INTERLEUKIN-18; EXPRESSION; HYPERTENSION;
D O I
10.1155/2010/841343
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The effect of candesartan, an angiotensin-II type-1 receptor antagonist, on the metabolic profile and renal inflammation is unclear. We evaluated this relationship by feeding male lean (LZ) and obese (OZ) Zucker rats chow or chow with candesartan (23.5mg/kg . diet) for 14 weeks (n = 6-8/treatment/body type). Candesartan reduced serum triglycerides, plasma creatinine, urine albumin, and renal cortical collagen and glycogen deposition in the OZ. An ELISA-based cytokine array revealed that candesartan normalized elevated renal interleukin (IL) 1-beta and monocyte chemoattractant protein-1 (MCP-1) levels in OZ. Nonetheless, candesartan impaired glucose tolerance, and did not lower blood insulin or glucose levels. Moreover, renal IL-1 alpha, -2, -4, -6 and -10 tumor necrosis factor-alpha, interferon-gamma, were significantly reduced in OZ relative to LZ, and increased by candesartan. Furthermore, candesartan increased growth-regulated oncogene, transforming growth factor-beta 1 and IL-18 in OZ kidneys to a level higher than LZ or untreated OZ. Candesartan did not affect renal cytokine levels in LZ. Overall, candesartan attenuated renal disease and improved renal function in OZ, despite mixed effects on metabolic factors and cytokines. Reduced plasma triglycerides and/or renal MCP-1 and IL-1 beta may have had a role in this protection. However, these effects were clearly independent of any improvement in glucose tolerance.
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页数:12
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