Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes.
BACKGROUND
Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats.


METHODS
The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls.


RESULTS
After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening.


CONCLUSIONS
Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.
Chang
K-C
KC
Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan. kcchang@ha.mc.ntu.edu.tw
Tseng
C-D
CD
Wu
M-S
MS
Liang
J-T
JT
Tsai
M-S
MS
Cho
Y-L
YL
Tseng
Y-Z
YZ
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood; D008297:Male; D011312:Pressure; D011673:Pulsatile Flow; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007328:Insulin; C004479:pimagedine