Effects of long-term treatment of aminoguanidine on the mechanical properties of the arterial system in a new model of streptozotocin-nicotinamide rats

• Main Authors: Yi-Li Cho, 卓怡利
• Other Authors: 張國柱
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/31016805604151523903

碩士 === 國立臺灣大學 === 生理學研究所 === 93 === A new experimental type 2 diabetic syndrome, which is closer to human non-insulin-dependent diabetes mellitus, has been reported in adult rats administered streptozotocin (STZ) and partially protected with a suitable dose of nicotinamide (NA). The accelerated formation of advanced glycation end products (AGEs) on long-lived connective tissue may account for some of the complications of diabetes such as stiffing of collagen, vascular narrowing, and arterial stiffing. In this study, we determined the effects of long-term treatment with aminoguanidine (AG), an inhibitor of AGEs formation, on hemodynamic parameters describing arterial wall elasticity and pulse wave reflection in STZ-NA diabetic rats. Rats at 2 months were given NA 180mg/Kg i.p., 30 mins before an intravenous injection of 50mg/Kg STZ . This STZ-NA rats before use, and compared with the untreated age-matched controls. Mean while, the STZ-NA diabetic rats were treated for 4 (STZ-NA4) and 8 weeks (STZ-NA8) with AG (daily peritoneal injections of 50 mg/kg) and compared with the untreated diabetic groups. At 180 mg/Kg, NA largely prevented STZ-induced body weight loss, hyperglycemia, and hypoinsulinemia in the rats with diabetes. In comparison with controls, the STZ-NA rats of 8 weeks but not 4 weeks after induction of diabetes showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance (Rp), at 54.9±2.5 versus 65.8±2.8mmHg•s•ml-1 (P＜0.05).The STZ-NA8 diabetes also contributed to an increase in aortic characteristic impedance (Zc), from 1.489±0.105 to 1.952±0.091 mmHg．s．ml-1 (P＜0.05) and a decrease in wave transit time (τ), from 25.8±1.2 to 20.6±0.91 ms (P＜0.05). The elevated Zc and the reduced τ suggest that STZ-NA8 diabetic rats may have a detrimental effect on aortic distensibility. Meanwhile, the heavy reflection intensity occurred in rats with STZ-NA of 8 weeks diabetes because of the diminished τ and the increased wave reflection factor (Rf) (0.49±0.03 versus 0.61±0.04, P＜0.05). After exposure to AG, the STZ-NA8 diabetic rats exhibited a significant improvement in physical properties of the resistance vessels, as evidenced by the reduction of 18.1﹪in Rp. Meanwhile, AG retarded the diabetes-induced decline in aortic distensibility, as reflected in the decrease of 18.7﹪ in Zc (P＜0.05) and the increase of 21.8﹪inτ(P＜0.05). AG also prevented the diabetes-induced augmentation in systolic loading condition for the left ventricle coupled to the arterial system, due to the increased τand the decreased Rf (-22.9﹪). Moreover, the ratio of LV weight to body weight was lowered by AG treatment, suggesting that the prevention of the diabetes-related cardiac hypertrophy may correspond to the drug-induced decline in LV systolic load. By contrast, AG exerted no effects on the mechanical properties of Winkessel vessels, as well as resistance vessels, in normal controls and STZ-NA of 4 weeks diabetes. We conclude that only rats with STZ-NA of 8 weeks diabetes produce a detrimental effect on the pulsatile nature of blood flows in arteries. Treatment with AG may impart significant protection against aortic stiffening in STZ-NA of 8 weeks diabetic rats possibly through inhibition of the AGEs-accumulation on collagen in the arterial wall.