The effect of chronic exercise on heart weights, succinate dehydrogenase (SDH) activities, and norepinephrine (NE) concentrations was examined in the Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats. Nine week old animals were trained either by forced treadmill running (26.8 m/min-1 hr/day) or voluntary exercise in running wheels (@9, 000 m/day at peak) for 12 wks. Male rats subjected to forced treadmill running program gained weight significantly more slowly than sedentary freely eating controls (p<0.01) . Heart ventricles of exercised groups in WKY rats were heavier than those of the sedentary controls (p<0.05) . Ratio of heart ventricle weight to body weight of male SHR and WKY rats was significantly higher in the runners than in the sedentary controls (p<0.01) . SDH activities of the red gastrocnemius muscle were 30 and 100% greater (p<0.01) for the voluntary and forced exercise animals, respectively, than the sedentary controls. Changes in muscle enzyme activity and heart weight were used to verify that the forced exercise program had produced a trained state. Blood pressure (BP) of voluntarily exercised SHR was 10% less at 15 wks (p<0.05) and remained lower until the end of training than that of control SHR, whereas BP of forced-trained SHR was not lowered. There was no measurable change in BP of WKY rats as a results of training. The voluntary exercise program had no effect on the concentrations of NE in heart and adrenal glands of SHR and WKY rats. The NE concentrations of heart and adrenal gland in forced/trained SHR and WKY rats were @10-40% greater than those of sedentary controls. The results of these experiments indicate that chronic exercise can depress the blood pressure of SHR rats. However, difference between two types of exercise training suggests that the endurance capacity improved by chronic exercise may not be a primary factor to delay the onset of the hypertention.

OBJECTIVESWe have attempted to upgrade and validate an in-house cDNA microarray system developed by our group for the evaluation of chemical toxicity.

METHODSTo establish an in-house microarray, we selected genes that play pivotal roles in detoxifying exogenous substances and maintaining homeostasis in the liver. To validate the system, we examined gene expression profiles in mouse liver following treatment with different doses of carbon tetrachloride (CCl(4)). The data were also analyzed by pathway analysis tools.

RESULTSWe upgraded our array system by collecting genes that are responsive to xenobiotic receptors, apoptosis-related genes, and stress-responsive genes. The acute toxicity of CCl(4) was confirmed by elevated levels of serum transaminase and histopathological findings. The microarray data showed the CCl(4) treatment induced significant changes in gene expression in the mouse liver, and the ingenuity pathways analysis revealed alterations in gene expression in inflammation-related networks.

CONCLUSIONSWe have established a focused microarray system that may be useful for use in toxicogenomics studies. Using this array system, we gained insight into the mechanisms by which CCl(4) exerts its toxic effects. The results of our study also indicate that the combination of focused arrays and bioinformatics tools is helpful in the mechanistic analysis of chemical toxicity.