Body's Internal Clock Controls Blood Pressure

The investigators found that genes relevant to the production and breakdown of catecholamines--a class of neurotransmitters secreted by the adrenal glands that includes adrenalin, norepinephrine, and dopamine--were under the control of the clock. Using a mouse model in which both catecholamines and BP were made to surge, the researchers found that the rise in both BP and catecholamines depended on the time of the stress; the greatest response occurred at a time that would correspond to the early morning hours in humans.

Surprisingly, when the investigators deleted a core clock gene completely, they managed to abolish both the catecholamine and blood pressure response to stress, irrespective of when the stress was applied during the daily clock cycle. This effect was specific to the catecholamines, as the stress response to corticosteroids was unaltered. The study was published in the February 27, 2007, issue of the Proceedings of the [U.S.] National Academy of Sciences (PNAS).

"These results integrate for the first time the two leading explanations for the diurnal variation in blood pressure and reveal an unexpected role for a clock gene in regulating the stress response,” said senior author Garret A. FitzGerald, M.D., director of the Institute for Translational Medicine and Therapeutics at Penn. "They raise the novel possibility of modifying blood pressure and consequently the early-morning risk of heart attack and stroke by using drugs to 'reset' the molecular clock.”

The molecular clock is a complex set of genes located in a discrete brain area that tightly regulate circadian rhythms in behavior, temperature, and metabolism. Researchers now appreciate that this master clock also interacts with clocks in almost all types of tissues.


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