Circadian periodicity in cerebral blood flow: Studies in normotensive and transgenic hypertensive rats

Cardiovascular parameters such as arterial blood pressure (ABP) and heart rate display pronounced circadian variation. In addition, evidence has been presented in favor of diurnal changes of perfusion in the heart, skin, kidney, and skeletal muscle. The present study was performed to detect whether there is a circadian periodicity in the regulation of cerebral perfusion. Normotensive Sprague Dawley rats (SDR, appr. 15 weeks old) and hypertensive (mREN2)27 transgenic rats (TGR, approximately 12 weeks old) were equipped in the abdominal aorta with a blood pressure sensor coupled to a telemetry system for continuous recording of systolic and diastolic ABP, heart rate, and locomotor activity. Five to twelve days later, a laser-Doppler flowmetry (LDF) probe was attached to the skull by means of a guiding device to measure changes of cerebral blood flow (CBF). After recovery from anesthesia, continuous measurements were taken for 3–5 days. The time series were analyzed with respect to the MESOR (midline estimating statistic of rhythm, i.e. the mean value of a given period), amplitude, and acrophase (i.e. the phase angle corresponding to the peak of a given period) of the 24 h period and subharmonics including 12 h, 8 h, 4.8 h and 4 h period length. All data are given as meanSD with the time indicated in 24 h format. The circadian rhythm was the most prominent one for each parameter throughout the experiments. In SDR the acrophases of systolic and diastolic ABP were at 04:12 h 42 min and 02:24 h 42 min, respectively. In the TGR the ABP signal showed its typical inverse pattern with the maximum of the ABP occurring during light on (acrophase of systolic ABP, 09:48 h 108 min; acrophase of diastolic ABP, 09:54 h 144 min), i.e. during the resting phase of the animals. The peak of the circadian periodicity in the LDF signal occurred around midnight in both, SDR (23:54 h 114 min) and TGR (00:48 h 78 min), i.e. during the subjective activity phase of the animals. The acrophase position of the LDF signal was consistently prior to that of the locomotor activity (SDR, 01:42 h 18 min; TGR, 1:18 h 66 min). The present data suggest the presence of a circadian periodicity in the regulation of cerebral perfusion. The generator of this periodicity is not yet known. The circadian rhythm in the LDF signal is independent from that of the ABP since it did not follow the inverse periodicity in TGR. It is probably also independent from locomotor activity since its peak occurred consistently prior to that of the locomotor activity. The presence of a circadian periodicity in the CBF may have implications for the occurrence of diurnal alterations of cerebrovascular events with a morning peak observed in humans.