Prevention of arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.
OBJECTIVE
Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.


METHODS
Diabetes was induced in rats by a single tail vein injection with 55 mg.kg(-1) steptozotocin (STZ). After induction of hyperglycaemia, animals were treated for 8 weeks with pyridoxamine (1 g.L(-1) in drinking water) and compared with the age-matched untreated diabetic controls. Pulse wave reflection along the vasculature was derived using the impulse response function of the filtered aortic input impedance spectra.


RESULTS
Treatment of this experimental diabetes with pyridoxamine resulted in a significant increase in wave transit time and a decrease in wave reflection factor, indicating that pyridoxamine attenuates the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, pyridoxamine therapy ameliorated the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Glycation-derived modification of aortic collagen was also found to be attenuated by administration of pyridoxamine to the STZ-induced diabetic rats.


CONCLUSIONS
Pyridoxamine imparts significant protection against the diabetes-induced deterioration in pulsatile arterial load imposed on the heart, at least partly through inhibition of the formation of advanced glycation end products and their accumulation on aortic collagen of the STZ-treated rats.
Chang
Kuo-Chu
KC
Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan. kcchang1008@ntu.edu.tw
Liang
Jin-Tung
JT
Tsai
Pei-Shan
PS
Wu
Ming-Shiou
MS
Hsu
Kwan-Lih
KL
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001158:Arteries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D008297:Male; D011673:Pulsatile Flow / Q000187:drug effects; D011733:Pyridoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D017127:Glycation End Products, Advanced; D011733:Pyridoxamine; D003094:Collagen
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