Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules — PNAS

http://www.pnas.org/cgi/content/abstract/0703388104v1

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

( cGMP phosphodiesterase | resynchronization | suprachiasmatic nuclei | phase advance )
Patricia V. Agostino, Santiago A. Plano, and Diego A. Golombek *

Laboratorio de Cronobiología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, 1876 Buenos Aires, Argentina

Communicated by Joseph A. Beavo, University of Washington School of Medicine, Seattle, WA, April 12, 2007 (received for review November 2, 2006)

Mammalian circadian rhythms are generated by a master clock located in the suprachiasmatic nuclei and entrained by light-activated signaling pathways. In hamsters, the mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase, cGMP and its related kinase (PKG). It is not completely known whether interference with this pathway affects entrainment of the clock, including adaptation to changing light schedules. Here we report that cGMP-specific phosphodiesterase 5 is present in the hamster suprachiasmatic nuclei, and administration of the inhibitor sildenafil (3.5 mg/kg, i.p.) enhances circadian responses to light and decreases the amount of time necessary for reentrainment after phase advances of the light-dark cycle. These results suggest that sildenafil may be useful for treatment of circadian adaptation to environmental changes, including transmeridian eastbound flight schedules.

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