Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA064

Poster Communications

Chronic phase advance shifts desynchronize endocrine rhythms and enhance responsivity of the cardiovascular system to norepinephrine in rats

M. Zeman1, M. Okuliarova1, L. Molcan1

1. Animal Physiology and Ethology, Comenius University Bratislava, Faculty of Natural Sciences, Bratislava, Slovakia.

Disturbances of circadian oscillations can have negative effects on cardiovascular functions but epidemiological data are inconclusive and new experimental data from animal experiments elucidating critical biological mechanisms are needed. We studied consequences of chronic phase advance shifts of light/dark (LD) cycle on the endocrine and cardiovascular system control. The study was approved by the local ethical committee and veterinary authority. In experiment 1, mature male rats were exposed either to the stable LD 12:12 (CONT, n=36) or rotating 8-h phase advance shifts of LD three times per week (SHIFT, n=36) for 10 weeks. Blood pressure (BP) was monitored weekly by plethysmography. Rats were killed under CO2 anaesthesia in 4-h intervals over 24 hours and daily rhythms of plasma melatonin, corticosterone and leptin were determined. In experiment 2, male rats (CONT, n=9 and SHIFT, n=5) were exposed to the identical LD treatment as in experiment 1 for 12 weeks and daily rhythms of BP and heart rate (HR) were measured by telemetry. Telemetry transmitters were implanted under ketamine (75mg kg-1) and xylazine (10mg kg-1, i.p.) anaesthesia. During week 12, animals were treated with norepinephrine (NE; 200 μg kg-1, s.c.) in the middle of the light and dark phase. Circadian rhythms were evaluated with Lomb-Scargle Periodogram by Chronos-Fit software. Effect of NE was evaluated as an area under the curve (AUC) using a trapezoidal rule. Data were analysed with repeated analysis of variance. We found preserved melatonin rhythms in SHIFT rats with damped amplitude in comparison with CONT suggesting that the central oscillator could adapt to chronic phase shifts, but its power was attenuated. Daily rhythms of corticosterone and leptin were present in CONT and disappeared in SHIFT rats suggesting that disturbances of the circadian system may occur down-stream of the central oscillator. SHIFT rats did not exhibit the BP increase as compared to CONT but disturbed circadian rhythms in BP and HR were observed. Administration of NE to CONT during the daytime resulted in a BP increase (+39%; 140 min) while saline increased BP only temporarily (+19%; 30 min). NE administration to CONT rats induced a higher increase of BP during the passive phase (+36%) in comparison with the active phase (+23%). In SHIFT rats we found a more pronounced response of BP after NE in comparison to CONT without difference between the passive (+35%) and active (+34%) phase. Our results revealed an internal desynchronization in the endocrine system and weakened circadian control of BP and HR under chronic phase advance shifts with a pronounced response to NE especially during the passive phase. We conclude that the attenuated circadian control can enhance a response of the cardiovascular system to sympathetic activation with a potential negative impact on physiology and behaviour.

Where applicable, experiments conform with Society ethical requirements