The Protective Effect of Ascorbic Acid on Exogenous Asymmetric Dimethylarginine Induced Intimal Thickness and Cholesterol Increase in Rats

Abstract

Introduction: The endothelium plays an important role in maintaining vascular structure and tonus; and endothelial cells are protective against the thrombosis and atherosclerosis. Cardiovascular risk factors, such as metabolic diseases, systemic and local inflammations, result in endothelial dysfunction. Nitric oxide is one of the endothelium derived substances that has an important role in maintaining the endothelial homeostasis. The asymmetric dimethylarginine (ADMA) is the endogenous inhibitor of the nitric oxide synthase. ADMA has been shown to impair the endothelial function and to be associated with hypercholesterolemia, hyperhomocysteinemia, and atherosclerosis. Ascorbic acid, a vitamin with reductant and antioxidant effects, can improve endothelial function and decrease the reactive oxygen species level. Our objective was to determine pathologically exogenous ADMA effect on endothelium of abdominal aorta, and to observe protective effect of antioxidant ascorbic acid. Materials and methods: The rats were divided in three groups: control, ADMA and ADMA + ascorbic acid. After administration of ADMA and ascorbic acid for 10 days, the blood was collected and abdominal aorta removed from the animals. Homocysteine, triglyceride, and cholesterol levels were measured by autoanalyzer. Abdominal aorta was evaluated histopathologically and the intimal thickness was measured using an imaging system. Result: The ADMA increased the intimal thickness (p=0.003), and ascorbic acid inhibited this increase (p=0.001). ADMA also increased the levels of triglyceride and cholesterol (p=0.008 and p=0.001), and the increased triglyceride and cholesterol levels are inhibited by ascorbic acid (p=0.000 and p=0.001). Conclusions: Increased intimal thickness by delivering exogenous ADMA supports that exogenous ADMA might be one of the factors resulting in atherosclerosis. We consider that the increase in intima thickness may not be a direct effect of ADMA but may be secondary to the increased cholesterol levels and ascorbic acid can be protective for atherosclerosis.