The effects of valsartan on the accumulation of circulating and renal advanced glycation end products in experimental diabetes.
BACKGROUND
Blockade of the RAS with the ACE inhibitor ramipril prevents the accumulation of advanced glycation end products (AGEs) in experimental diabetes. Although AT1 receptor antagonists may inhibit AGE formation in vitro, their effect in normotensive animals with type 1 diabetes has not been established.


METHODS
Streptozotocin-induced diabetic and control animals were randomized (N=10/group) to receive the AT1 antagonist valsartan at a dose of 30 mg/kg/day by oral gavage for 24 weeks, or no intervention. Renal and plasma AGE accumulation was correlated with renal functional parameters.


RESULTS
Valsartan reduced the albumin excretion rate consistent with its renoprotective effects. Renal and skin collagen accumulation of the non-fluorescent AGE carboxymethyllysine (CML) were increased in animals with diabetes, but normalized following treatment with valsartan. Renal fluorescence and skin collagen pentosidine levels were also increased by diabetes. However, valsartan only provided a modest attenuation of these parameters. In addition, diabetes was associated with increased plasma fluorescence, which was unaffected by AT1 antagonism.


CONCLUSIONS
Renoprotective doses of valsartan are associated with a significant reduction in the accumulation of tissue and plasma CML. These effects were not the same for all AGEs, suggesting combination approaches will be required to optimize renoprotection in diabetes.
Forbes
Josephine M
JM
Danielle Alberti Memorial Centre for Diabetes Complications, Wynn Domain, Baker Heart Research Institute, Melbourne, Australia. Josephine.Forbes@baker.edu.au
Thomas
Merlin C
MC
Thorpe
Suzanne R
SR
Alderson
Nathan L
NL
Cooper
Mark E
ME
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000068756:Valsartan
D000959:Antihypertensive Agents; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine