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Cardiovascular system holds a key to circadian clock

Blood pressure varies in all of us throughout the day. This pattern, circadian variability, is exaggerated in patients who have high blood pressure, suggesting that the mechanisms which control this rhythm are disturbed.

Indeed, this altered biorhythm seems to have clinical consequences. Heart attacks and strokes occur most commonly early in the morning when blood pressure is at its highest point in its 24 hour cycle. Scientists at the University of Pennsylvania School of Medicine have discovered another key to the body's circadian clock that may begin to explain these observations and lead to new treatments based on the body's timing mechanism.

Their discovery, which provides the first evidence for how hormones and vitamins can reset the human circadian clock, shows in detail how activation of vitamin A receptors can regulate the rhythm of the clock. This provides an important clue to how the master clock, which lies deep in the brain, can regulate distal organs, such as the liver, kidney and muscle by controlling clocks throughout the body.

The Penn study establishes that blood vessels contain their own peripheral circadian system, similar to clocks in other organs.

Also, significantly, it links hormonal and vitamin control for the first time to the circadian rhythms that control body temperature, sleep and wakefulness , pain sensitivity, and the response to drugs.

"We know that the responseto certain drugs used in the treatment of cancer vary substantially depending on the time of day that they are administered," said Garret FitzGerald, MD, chairman of Penn's Department of Pharmacology and author of the study. "However, this work elucidates a molecular mechanism which permits a refinement of such chronopharmacology. Resetting the clock might have obvious application in the treatment of jet lag, but could also combine with existing knowledge to adjust circadian variability in drug response to the ne
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Contact: Ellen O'Brien
ellen.obrien@uphs.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
28-Jun-2001


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