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

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.
AuthorsV Senses, S Ozyazgan, E Ince, M Tuncdemir, F Kaya, M Ozturk, G Sultuybek, A G Akkan
JournalJournal of basic and clinical physiology and pharmacology (J Basic Clin Physiol Pharmacol) Vol. 12 Issue 3 Pg. 227-48 ( 2001) ISSN: 0792-6855 [Print] England
PMID11762693 (Publication Type: Journal Article)
Chemical References
  • Blood Glucose
  • Ribonucleosides
  • Nitroprusside
  • Aminoimidazole Carboxamide
  • acadesine
  • Acetylcholine
  • Norepinephrine
  • 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)

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