Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis.
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.
['Satheesan|S|S|', 'Figarola|J L|JL|', 'Dabbs|T|T|', 'Rahbar|S|S|', 'Ermel|R|R|']
D000818:Animals D001011:Aorta D001794:Blood Pressure D002087:Butyrates D006332:Cardiomegaly D003094:Collagen D003187:Compliance D003921:Diabetes Mellitus, Experimental D003925:Diabetic Angiopathies D006442:Glycated Hemoglobin A D017127:Glycation End Products, Advanced D007004:Hypoglycemic Agents D008297:Male D017207:Rats, Sprague-Dawley D000067759:Receptor for Advanced Glycation End Products D011971:Receptors, Immunologic D013997:Time Factors D014280:Triglycerides D014655:Vascular Resistance D059289:Vascular Stiffness
LR-90 Advanced glycation end products aortic distensibility aortic characteristic impedance wave reflection factor wave transit time