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International Journal of Experimental Diabetes Research
Volume 1 (2000), Issue 2, Pages 145-153

Impaired Relaxation in Aorta from Streptozotocin-diabetic Rats: Effect of Aminoguanidine (AMNG) Treatment

University of Istanbul, Cerrahpasa Faculty of Medicine, Department of Pharmacology, Istanbul 34303, Turkey

Received 27 September 1999; Accepted 10 February 2000

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aim The effect of 8 weeks′ streptozotocin (STZ)- induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigated in vitro.

Materials and Methods Studies were performed in untreated control rats (n = 10), STZ-induced (60 mg/kg i.v.) diabetic rats (n = 10), AMNG-treated (600 mg/l given in drinking water throughout 8 weeks) control rats (n = 10) and AMNG-treated (600 mg/l given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n = 10). Results are expressed as the mean ±s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparisons test.

Results 1. The decreased body weights (205 ± 6 g) and increased blood glucose levels (583 ± 8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 ± 6 g, p < 0.05 and 480 ± 14 mg/dl, p < 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p < 0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 ± 8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 ± 4%). 3. Neither diabetes nor treatment affected endothelium-independent relaxation (pD2 and max. Relax.) to sodium nitroprusside. 4. Vasoconstrictor responses (pD2 and Max. Contraction) to noradrenaline and KCl were not influenced by the diabetic state and treatment.

Conclusion Our data suggest that 8 weeks of experimental diabetes is associated with a decreased endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced endothelial dysfunction. This may be mediated via the prevention of advanced glycosylation end product formation, the enhanced release of vasodilator substances such as prostacyclin, the increased elasticity of blood vessels, the antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.