Effect of 5-aminoimidazole-4-carboxamide riboside (AICA-r) on isolated thoracic aorta responses in streptozotocin-diabetic rats.

Abstract

Diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. 5-amino-4-imidazole-carboxamide riboside (AICA-r), a nucleoside corresponding to AICA-ribotide and an intermediate of the de novo pathway of purine biosynthesis, was recently proposed as a new insulinotropic tool in non-insulin-dependent diabetes mellitus. The aim of the present study was to define whether AICA-r affects altered vascular responsiveness to vasoconstrictors and vasodilators in the thoracic aorta of neonatal streptozotocin (STZ)-diabetic rats. The results of this study indicate that a 1-month treatment with AICA-r significantly increases the body weight in diabetic rats; significantly decreases the blood glucose level of diabetic rats (from 302+/-47 to 135+/-11 mg/dL, p<0.001); does not significantly affect the fast, slow, and total components of responses to noradrenaline in all the experimental groups; reverses the increased Emax values of noradrenaline in diabetic rats to near-control values; reverses the completely abolished responses of acetylcholine (pD2 and percent relaxation) in diabetic rats to control values; and reverses the decreased pD2 values of sodium nitroprussiate in diabetic rats to control values. In conclusion, AICA-r treatment in neonatal STZ-diabetic rats improved increased blood glucose levels, accelerated weight gain, reversed endothelial dysfunction, and normalized vascular responses.

• Authors: V Senses, S Ozyazgan, E Ince, M Tuncdemir, F Kaya, M Ozturk, G Sultuybek, A G Akkan
• Journal: Journal of basic and clinical physiology and pharmacology (J Basic Clin Physiol Pharmacol) Vol. 12 Issue 3 Pg. 227-48 ( 2001) ISSN: 0792-6855 [Print] Germany
• PMID: 11762693 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Ribonucleosides
• Nitroprusside
• Aminoimidazole Carboxamide
• acadesine
• Acetylcholine
• Norepinephrine

Topics

• Acetylcholine (pharmacology)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Animals
• Aorta, Thoracic (drug effects, physiology)
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, physiopathology)
• Endothelium, Vascular (physiology)
• Female
• Injections, Intraperitoneal
• Male
• Nitroprusside (pharmacology)
• Norepinephrine (pharmacology)
• Rats
• Rats, Wistar
• Ribonucleosides (pharmacology)
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)