Chronic stress-induced oxidative damage and hyperlipidemia are accompanied by atherosclerotic development in rats

Although stress-induced hyperlipidemia and increased oxidative stress have been reported and implicated in etiology of atherosclerosis, experimental evidence for stress-induced atherosclerotic development concomitant with these alterations is lacking. In this study, exposure of adult male albino Wistar rats (Rattus norvegicus) to restraint for 1 h and after a gap of 4 h to forced swimming for 15 min every day for 2, 4, or 24 weeks resulted in a duration of exposure-dependent hyperlipidemia as shown by significant increases in concentrations of blood cholesterol, low-density lipoproteins, and triglycerides and decrease in high-density lipoprotein concomitant with increased oxidative stress as indicated by decrease in hepatic antioxidant enzyme activities and increase in lipid peroxidation in the liver, kidney, and heart. These alterations were accompanied by development of fibrous layer, formation of foam cells, reduction in elastic fibers, and accumulation of Oil-Red-O-positive lipid droplets in the intima of thoracic aorta following 24 weeks of stress exposure, but not after 4 weeks. The study demonstrates for the first time that (i) chronic stress-induced hyperlipidemia and oxidative damage are coupled with atherosclerotic development in rats fed with normal diet and (ii) chronic stress effects prevail even after the cessation of stress exposure as indicated by high concentration of blood cholesterol and reduced hepatic superoxide dismutase activity 20 weeks after 2 or 4 weeks of stress. This study exemplifies long-term allostatic regulation leading to a pathological state, with long-term hyperlipidemia and oxidative damage from chronic stress resulting in atherosclerosis.