The leading drug prescribed for male impotence can counteract the lethargy caused by a disruption in the sleep cycle, a study in rodents suggests. Sildenafil, commonly known as Viagra, helps hamsters rebound from a 6-hour clock change such as a long eastbound plane flight produces.
To mimic conditions that can lead to jet lag, scientists habituated hamsters to a daily routine of 14 hours of light and 10 hours of darkness. The researchers then abruptly switched on the lights 6 hours early and continued the same light-to-dark routine from that point onward, simulating the effects of a flight from Chicago to London.
Just before changing the hamsters' routine, the researchers injected each animal with either sildenafil or saline solution. Then, they observed how long it took the hamsters to restart their daily habit of running on a wheel.
Hamsters receiving a large single dose of sildenafil resynchronized their body clocks and resumed their usual wheel routines within 6 days. Hamsters getting a lower dose took 8 days, whereas those receiving the inert injection took 12 days, the scientists report in the June 5 Proceedings of the National Academy of Sciences.
Circadian rhythm in mammals is controlled mainly by neurons in the hypothalamus, says study coauthor Patricia V. Agostino, a neuroscientist at the National University of Quilmes in Bernal, Argentina. When the vision system detects light, it sends stimuli to the hypothalamus and sets off a series of events that generate wakefulness. "Light is the main synchronizer of the circadian clock," Agostino says.
A compound called cyclic guanine monophosphate (cyclic GMP) plays a role in regulating circadian rhythm. In the hamster study, scientists measured the animals' blood concentrations of cyclic GMP 45 minutes before changing the light-dark schedule. Compared with hamsters receiving saline shots, the animals injected with sildenafil had double the amount of cyclic GMP. Sildenafil shuts down enzymes that would limit cyclic GMP production, but Agostino's team isn't certain that this is how the drug restores circadian rhythm.
"This resetting of the clock seems to be novel," says pharmacologist Joseph A. Beavo of the University of Washington School of Medicine in Seattle. He cautions that the new research is only on rodents, but since sildenafil is a widely used drug, a sampling of men who travel frequently and take it might turn up any stabilizing effect on circadian rhythm, he says.
Most travelers who experience jet lag find that the effects are strongest after an eastbound flight, which shortens the day and pushes the circadian clock forward. Interestingly, sildenafil's circadian readjustment worked only in animals whose circadian rhythms had been advanced, Agostino says. That suggests that the drug would work for eastbound travelers and airline personnel, as well as some shift workers, she says.
Patricia V. Agostino
Department of Science and Technology
National University of Quilmes
Roque S. Peña 352
Bernal, 1876 Buenos Aires
Joseph A. Beavo
T-471 Health Sciences Center
University of Washington
School of Medicine
Seattle, WA 98195
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