Drug Design, Development and Therapy (Dec 2015)
Effects of vitamin C treatment on collar-induced intimal thickening
Abstract
Mehmet Zuhuri Arun,1 Levent Üstünes,1 Gülnur Sevin,1 Erdener Özer2 1Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Department of Pathology, School of Medicine, Dokuz Eylül University, Izmir, Turkey Abstract: Vitamin C has efficient antioxidant properties and is involved in important physiological processes such as collagen synthesis. As such, vitamin C deficiency leads to serious complications, including vascular diseases. The aim of this study was to investigate the effects of vitamin C treatment on collar-induced intimal thickening. Rabbits were fed a normocholesterolemic diet and a non-occlusive silicon collar was placed around the left carotid artery for 3, 7, and 14 days. The rabbits were treated with or without vitamin C (150 mg/kg/day). Collar-induced intimal thickening became apparent at day 7. The effect of the collar on intimal thickening was more prominent at day 14. Vitamin C treatment significantly inhibited collar-induced intimal thickening at day 14. The placement of the collar around the carotid artery decreased maximum contractile responses against contractile agents (KCl, phenylephrine, 5-hydroxytryptamine). The effect of the collar on contractile responses was enhanced as days elapsed. Decreased contractile responses of collared carotid arteries normalized at day 14 in the vitamin C treatment group. Vitamin C treatment also restored sensitivity to phenylephrine. The collar also significantly decreased acetylcholine-induced relaxations at day 3 and day 7. Acetylcholine-induced relaxations normalized in collared-arteries in the placebo group at day 14. Vitamin C treatment significantly increased acetylcholine-induced relaxations of both normal and collared carotid arteries at day 14. MMP-9 expression increased in collared arteries at day 3 and day 7 but did not change at day 14. MMP-2 expression increased in collared arteries at day 14. However, vitamin C treatment reduced collar-stimulated expression of MMP-2 at day 14. These findings indicate that vitamin C may have potentially beneficial effects on the early stages of atherosclerosis. Furthermore these results, for the first time, may indicate that vitamin C can also normalize decreased contractile response through perivascular collar placement. Keywords: vitamin C, collar, intimal thickening, rabbit carotid artery, vascular reactivity, MMP
