الفهرس | Only 14 pages are availabe for public view |
Abstract Hypercholesterolemia has emerged as a strong risk factor for cardiovascular disease (CVD), as it is associated with endothelium which is characterized by a shift of the actions of the endothelium toward reduced vasodilation. Mechanisms that participate in the reduced vasodilatory responses in endothelial dysfunction include reduced production of endothelium derived relaxing factors (EDRFs) as NO, prostacyclin and reduced production of endothelium derived hyperpolarizing factors(EDHFs) as epoxyeicosatrienoic acids (EETs). Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium. They are important regulators of vascular and they attenuate the inflammatory signaling pathways in both the endothelium and vascular smooth muscle, so they are considered to be endogenous protective factors against atherosclerosis, hypertension and other vascular diseases. Hydration of EETs by the soluble epoxide hydrolase (sEH) is the major route of their degradation to the less bioactive diols which are dihydroxyeicosatrienoic acids (DHETs). sEH inhibitors (sEHI) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA)stabilize EETs and enhance their beneficial effects suggesting their potential therapeutic role in reduction of endothelial dysfunction associated with hypercholesterolemia. The present work aimed to study the effect of soluble epoxide hydrolase inhibition on endothelial function in hypercholesterolemic rats. The duration of this study was 18 weeks and it was carried on 40 adult male albino rats, with body weight of 100±20 gm. 10 rats were fed on standard rat chow in control group (group I), 30 rats were fed on high cholesterol (HC) diet using a slight modification of Matos diet for 8 weeks to induce hypercholesterolemic model (group II). After confirmation of hypercholesterolemia by measuring total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels by homogenous assay, hypercholesterolemic rats were divided randomly into 2 equal groups each of 15 rats. |