Effects of melatoninergic agonists on light-suppressed circadian rhythms in rats.
This study addressed the question whether light-suppressed circadian rhythms in cardiovascular parameters in rats could be restored by melatonin and a synthetic analogue. Blood pressure, heart rate, and locomotor activity were monitored by radiotelemetry in six Sprague-Dawley rats. After synchronization to a 12:12 light/dark (LD) schedule (lights on at 0700 hours, 100 lux), rats were kept in constant light (LL) of low intensity (5-10 lux) for 11 weeks. After 3 weeks of LL, rats received daily intraperitoneal (i.p.) injections at 1900 hours of vehicle, the melatonin agonist S-21767 (5 mg/kg) and melatonin (1 mg/kg). Spectral power, 24-h amplitudes and the differences between day and night means were calculated as measures of circadian rhythmicity. During LL a lengthening of the endogenous period to 26 h was observed, which was accompanied by a continuous decrease in circadian amplitude in all parameters monitored until, in the third week of LL, circadian rhythmicity was almost abolished. Neither vehicle, S-21767 nor melatonin were able to restore circadian rhythms in blood pressure and locomotor activity. In contrast, both agonists induced circadian rhythmicity in heart rate in two out of six rats. The day/night difference in heart rate of all animals was significantly increased by S-21767 and, to a smaller extent, by melatonin, whereas the circadian amplitude was not affected. In conclusion, melatonin and the synthetic agonist were able to partially synchronize circadian rhythmicity in heart rate during constant light, but could not restore circadian rhythms in blood pressure.
Witte
K
K
Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine Mannheim, Ruprecht-Karls-University Heidelberg, Germany. witte@rumms.uni-mannheim.de
Grebmer
W
W
Scalbert
E
E
Delagrange
P
P
Guardiola-Lemaître
B
B
Lemmer
B
B
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects*; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000819:agonists* / Q000096:biosynthesis / Q000494:pharmacology*; D017440:Photoperiod; D051381:Rats; D017207:Rats, Sprague-Dawley
D008550:Melatonin