Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes

• Published in: European journal of clinical investigation Vol. 36; no. 8; pp. 528 - 535
• Main Authors: Chang, K.-C., Tseng, C.-D., Wu, M.-S., Liang, J.-T., Tsai, M.-S., Cho, Y.-L., Tseng, Y.-Z.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2006; Blackwell
• Subjects: Advanced glycation end-products; aminoguanidine; Animals; Aorta - drug effects; Aorta - physiopathology; aortic input impedance; Biological and medical sciences; Blood Glucose - analysis; Body Weight - drug effects; Cardiac Output - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - administration & dosage; Etiopathogenesis. Screening. Investigations. Target tissue resistance; General aspects; Glycation End Products, Advanced - antagonists & inhibitors; Guanidines - administration & dosage; Heart Rate - drug effects; Injections, Intraperitoneal; Insulin - blood; Male; Medical sciences; Pressure; Pulsatile Flow; pulse wave reflection; Rats; Rats, Wistar; streptozotocin-nicotinamide diabetic rats; Stroke Volume - drug effects; Vascular Resistance - drug effects; Endocrinopathy; Antineoplastic agent; Type 2 diabetes; Animal model; Advanced glycation end-products; Rat; B-Vitamins; Arterial pulse; Glycation; Prevention; streptozotocin-nicotinamide diabetic rats; Aorta; Advanced stage; aortic input impedance; Streptozotocin; pulse wave reflection; Aminoguanidine; Rodentia; Metabolic diseases; Artery; Medicine; Vertebrata; Antibiotic; Mammalia; Animal; Nicotinamide; Impedance; Degradation product
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2006.01672.x

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. Materials and 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.