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


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.


CONCLUSIONS
AGM-treatment could improve the increased blood glucose level, reverse the endothelial dysfunction and normalize the endothelium-dependent relaxation responses in STZ-diabetic rats.
Ozyazgan
S
S
Department of Pharmacology and Clinical Pharmacology, Cerrahpasa Faculty of Medicine, University of Istanbul, 34750, Istanbul, Turkey.
Bicakci
B
B
Ozaydin
A
A
Denizbasi
A
A
Unluer
E E
EE
Akkan
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
D001786:Blood Glucose; D045462:Endothelium-Dependent Relaxing Factors; D000376:Agmatine; D000109:Acetylcholine