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.
Senses
V
V
Department of Pharmacology, Cerrahpasa Faculty of Medicine, University of Istanbul, Turkey.
Ozyazgan
S
S
Ince
E
E
Tuncdemir
M
M
Kaya
F
F
Ozturk
M
M
Sultuybek
G
G
Akkan
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012263:Ribonucleosides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D001786:Blood Glucose; D012263:Ribonucleosides; D009599:Nitroprusside; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D000109:Acetylcholine; D009638:Norepinephrine