title: Effects of a long-term treatment with an antioxidant pyridoindole on vascular responsiveness in diabetes-induced aging rats.
abstract: Impaired vascular reactivity is a hallmark of cardiovascular diseases induced by diabetes, which is also an accelerated aging model. This study was designed to investigate the effect of chronic treatment of stobadine, a pyridoindole antioxidant, on vascular responsiveness in diabetic animals. Age- (13-week old) and gender-matched Wistar rats were randomly divided into control and diabetic groups. Streptozotocin (55mg/kg, i.p.) was used to induce experimental diabetes. After induction of diabetes, rats were randomly assigned for receving stobadine (24.7 mg/kg/day, p.o.) or vehicle for 8-10 months. Stobadine treatment significantly reduced the severity of hyperglycemia, heart and kidney weights, systolic blood pressure, and attenuated diabetes-induced loss in body weight gain. Increased vasoconstriction responses to phenylephrine (PE; 10(-8)-10(-5) M) and BayK-8644 (3x10(-7)-3x10(-5) M) were significantly decreased by stobadine treatment in diabetes. Although stobadine treatment increased acetylcholine (ACh; 10(-9)-10(-5) M)-induced relaxation responses, sodium nitroprusside (10(-11)-10(-6) M)-induced relaxations were not affected by the treatment or diabetes. Stobadine treatment markedly reduced A23187 (10(-9)-3x10(-6) M)-induced relaxation responses while it remained unchanged in diabetics compared to controls. The transient vasoconstriction to PE was reduced by cyclopiazonic acid (10(-6) M) or thapsigargin (TH; 10(-6) M) in all groups. TH also inhibited the relaxation to ACh (3x10(-6) M) in control and stobadine-treated diabetic groups. These results suggest that antioxidative and Ca(2+) current regulatory effects of stobadine, contribute to the mechanisms responsible for its beneficial effects in aged diabetic rats.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey. aceylani@uwyo.edu
authors.forename: Asli F
authors.initials: AF
authors.lastname: Ceylan-Isik
authors.forename: Nuray
authors.initials: N
authors.lastname: Ari
authors.forename: Milan
authors.initials: M
authors.lastname: Stefek
authors.forename: Ruzena
authors.initials: R
authors.lastname: Sotnikova
authors.forename: Gülgün
authors.initials: G
authors.lastname: Ozansoy
authors.forename: Lubica
authors.initials: L
authors.lastname: Horakova
authors.forename: Çimen
authors.initials: Ç
authors.lastname: Karasu
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D002120:Calcium Channel Agonists; D061207:Calcium Ionophores; D002243:Carbolines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C100106:dicarbine