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: Asli F Ceylan-Isik, Nuray Ari, Milan Stefek, Ruzena Sotnikova, Gülgün Ozansoy, Lubica Horakova, Çimen Karasu
• Journal: Current aging science (Curr Aging Sci) Vol. 4 Issue 2 Pg. 150-7 (Jul 2011) ISSN: 1874-6128 [Electronic] United Arab Emirates
• PMID: 21235493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Blood Glucose
• Calcium Channel Agonists
• Calcium Ionophores
• Carbolines
• Vasoconstrictor Agents
• Vasodilator Agents
• dicarbine

Topics

• Age Factors
• Aging
• Animals
• Antioxidants (pharmacology)
• Aorta, Thoracic (drug effects, metabolism, physiopathology)
• Blood Glucose (drug effects, metabolism)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Calcium Channel Agonists (pharmacology)
• Calcium Ionophores (pharmacology)
• Calcium Signaling (drug effects)
• Carbolines (pharmacology)
• Diabetes Mellitus, Experimental (drug therapy, metabolism, physiopathology)
• Diabetic Angiopathies (drug therapy, metabolism, physiopathology)
• Dose-Response Relationship, Drug
• Rats
• Rats, Wistar
• Time Factors
• Vasoconstriction (drug effects)
• Vasoconstrictor Agents (pharmacology)
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)