title: Treated effect of silymarin on vascular function of aged rats: Dependant on nitric oxide pathway.
abstract: Abstract Context: Aging leads to endothelial dysfunction and vascular stiffness which are the main causes of many cardiovascular diseases. Previous reports have shown that the cell protective effect of silymarin (SM) is dependent on its antioxidant properties. Objectives: We investigated the effect of SM on vascular functions of aged rats and the involvement of nitric oxide or cyclooxygenase (COX) activity in this effect. Materials and methods: Isolated rat aortas were obtained from 22-month old rats. Each ring was incubated with SM (50 mg/L), SM/l-nitro-arginine methyl ester (100 μM, l-NAME) or SM/indomethacin (10 μM, INDO) in tissue bath. Three- to four-month-old rats were used as young controls. Endothelium-intact rings were precontracted with α-receptor agonist phenylephrine (0.001-30 µM) or voltage-dependent high potassium (40 mM), endothelium dependent/independent relaxant responses were obtained using acetylcholine (0.001-30 µM) and sodium nitroprusside (0.0001-3 µM), respectively. Results: Aging increased phenylephrine sensitivity (6.45 ± 0.08; 6.88 ± 0.09) and decreased KCl contraction (882 ± 118.4; 499 ± 80.4). SM treatment decreased the Emaxof both agents (548 ± 109; 223 ± 48.9). Aging deteriorated acetylcholine relaxation (93.9 ± 2.09; 72.0 ± 2.56) and SM improved the response (86.3 ± 1.90). l-NAME prevented the SM effect whereas INDO was ineffective. Discussion and Conclusion: Immediate SM treatment partially restored endothelial dysfunction and vascular tone in aging. The possible mechanism might not be mediated by prostacyclin or the COX pathway in acute administration; the nitric oxide pathway and calcium antagonistic features of SM relate to its action on the vessel.
authors.affiliation: Department of Medical Pharmacology, Medical Faculty, Adnan Menderes University , Aydin , Turkey and.
authors.forename: Buket
authors.initials: B
authors.lastname: Demirci
authors.forename: Omer
authors.initials: O
authors.lastname: Demir
authors.forename: Turhan
authors.initials: T
authors.lastname: Dost
authors.forename: Mustafa
authors.initials: M
authors.lastname: Birincioglu