Disturbances of endogenous circadian rhythms may result in adverse effects on metabolic and cardiovascular processes and participate in a higher incidence of diseases in shift workers. Physiological mechanisms underlying negative effects of chronodisruption are not completely understood and animal studies are needed for identifying key negative factors. In our study, in two independent experiments, we exposed mature male Wistar rats to repeated 8h phase advance shifts (PAS) of light/dark (LD) regimen (3 shifts per week) for12 weeks. In the first experiment blood pressure (BP), heart rate (HR) and locomotor activity (LA) were measured by radiotelemetry (Data Sciences Inc. USA) in 12 rats. Pressure sensor (TA11PA-C40) was implanted into the abdominal aorta under ketamine (75mg kg-1)/xylazine (10mg kg-1, i.p.) anaesthesia. Two weeks after surgery HR, BP and LA were monitored one week under control LD12:12 and then on week 1, 5, 10 and 11 of PAS exposure. Data were recorded continuously in 30s intervals over 24 hours (Dataquest ART 4.1, DSI). In the second experiment, male rats were exposed either to PAS (n=36) or control LD12:12 (n=36) and after 12 weeks they were killed by decapitation under CO2 anaesthesia in regular 4h intervals over 24 hours. Melatonin and corticosterone were measured by radioimmunoassay in plasma and melatonin was measured also in the pineal gland, heart and kidney. Clock gene (Bmal1 and per2) expression was measured by real time PCR in the heart. Data were evaluated with Cosinor analysis and ANOVA. As expected, higher values of BP, HR and LA were observed during the dark than the light phase of the day under control LD conditions. Circadian rhythms of BP, HR and LA were desynchronized in rats after exposure to repeated PAS but we did not find an increase of BP values. A transitory increase of absolute values in BP and HR was recorded only during the first week of phase shifts. Both mesor (1273 vs. 772 pg/gland) and amplitude (1554 vs. 611 pg/gland) of melatonin rhythm were damped in the pineal gland of PAS animals as compared to controls and no rhythmic changes were found in the plasma of PAS rats. The melatonin rhythm in the heart of PAS rats was damped and its acrophase was phase advanced by 4h in comparison with controls. Circadian rhythms of both clock gene expression in the heart were suppressed but in the phase with controls. Plasma corticosterone rhythm was found in controls but was absent in PAS rats in which high levels persisted during the passive phase of the day. We conclude that under repeated and frequent phase advanced shifts the circadian system is damped, animals may lose their ability to predict regular environmental loads with negative consequences on health in stressful environment.