The effect of chronic candesartan therapy on the metabolic profile and renal tissue cytokine levels in the obese Zucker rat.
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 (23.5 mg/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-1alpha, -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-beta1 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-1beta may have had a role in this protection. However, these effects were clearly independent of any improvement in glucose tolerance.
Ecelbarger
Carolyn M
CM
Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington, DC 20057, USA.
Rash
Arjun
A
Sinha
Rajesh K
RK
Tiwari
Swasti
S
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D016207:Cytokines / Q000378:metabolism*; D004032:Diet; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D013777:Tetrazoles / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016207:Cytokines; D013777:Tetrazoles; C081643:candesartan