Article date: June 2014
By: S Satheesan, J L Figarola, T Dabbs, S Rahbar, R Ermel in Volume 171, Issue 12, pages 3103-3114
Background and Purpose
We determined the effects of treatment with LR‐90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)‐induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR‐90 on the progression of aortic pathology.
Experimental Approach
STZ‐induced diabetic rats were treated with or without LR‐90 (50 mg L‐1 in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross‐linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra.
Key Results
LR‐90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR‐90 did not affect arterial BP, but prevented the diabetes‐induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR‐90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR‐90 inhibited collagen cross‐linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats.
Conclusions and Implications
Treatment with LR‐90 may impart significant protection against diabetes‐induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications.
DOI: 10.1111/bph.12656
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