The effect of agmatine on the vascular reactivity in streptozotocin-diabetic rats

Pharmacol Res. 2003 Aug;48(2):133-8. doi: 10.1016/s1043-6618(03)00101-4.

Abstract

Aim: We investigated the vascular effects of agmatine (decarboxylated arginine=AGM), an endogenous ligand for alpha(2)-adrenoceptors and imidazoline receptors, present in endothelium and smooth muscle, using the diabetic rat aortae.

Materials and methods: Studies were performed in control group (0.2 ml i.p. saline, n=10), streptozotocin (STZ)-diabetic control group (60 mg kg(-1) STZ i.p., n=10), agmatine (AGM)-control group (5 mg kg(-1)day(-1) i.p. AGM for 1 month, n=10), citrate-control group (0.2 ml 0.01 M, n=10), insulin-treated diabetic group ((3 U kg(-1) NPH+1 U kg(-1) regular insulin) twice per day, for 1 month, n=10) and AGM-treated diabetic group (5 mg kg(-1)day(-1) i.p. for 1 month, n=10). All values are expressed as means+/-S.E.M. Statistical analysis of the data was performed using ANOVA followed by Tukey multiple comparisons test.

Results: One-month AGM-treatment significantly decreased the blood glucose levels of diabetic rats (502+/-44 mg dl(-1) to 343+/-31 mg dl(-1), P<0.001). Fast, slow and total components of responses to noradrenaline in all the experimental groups were not significantly affected by AGM-treatment. AGM reversed the decreased responses of acetylcholine (pD(2) and Inh.%, P<0.001 and P<0.05) in diabetic rats although it did not affect the responses of sodium nitroprusside in all groups. The contraction values of KCl in all groups were not affected by AGM-treatment.

Conclusion: AGM-treatment could improve the increased blood glucose level, reverse the endothelial dysfunction and normalize the endothelium-dependent relaxation responses in STZ-diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Agmatine / pharmacology*
  • Agmatine / therapeutic use
  • Analysis of Variance
  • Animals
  • Aorta / drug effects
  • Aorta / physiology
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dose-Response Relationship, Drug
  • Endothelium-Dependent Relaxing Factors
  • In Vitro Techniques
  • Muscle Contraction / drug effects*
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Vasoconstriction / drug effects

Substances

  • Blood Glucose
  • Endothelium-Dependent Relaxing Factors
  • Agmatine
  • Acetylcholine