Tick tock: Circadian rhythm research

Tick tock

Could the body’s internal clock system influence blood pressure?

By Laura Mize
Preventing high blood pressure is pretty straightforward, right? Eat a nutritious diet with limited sodium, exercise regularly, don’t smoke, moderate alcohol use and maintain a healthful weight.

For some people, the equation is much more complex.

Michelle Gumz, Ph.D., an assistant professor in the UF College of Medicine department of medicine’s division of nephrology, hypertension and renal transplantation, explores how the body’s internal clocks affect the kidney and, in turn, blood pressure. It’s a niche not many people are studying. This year she led a team of other researchers to make what could be a big step forward in the field.

The group focused on whether a protein called “Period 1,” a natural component of the body’s internal clock systems, is linked to blood pressure in mice.

The answer seems to be “yes.” In an experiment Gumz and her team performed, mice without the protein had lower blood pressure than those that had it. Gumz said the findings surprised her, especially since all of the mice were on a healthful diet.

Could Period 1 really explain the difference in blood pressure? It’s possible, she said.

“Our data now suggests that Period 1 is involved in driving sodium reabsorption in the kidney, which contributes to blood pressure regulation,” Gumz said.

Another possibility is that Period 1 somehow contributes to “non-dipping,” an unscientific term for blood pressure that stays at daytime levels overnight, instead of sinking as it should. People who experience this phenomenon have greater risk of cardiovascular disease.

Hypertension, the journal of the American Heart Association, published an article online in April detailing the team’s findings. If Period 1 is a factor in high blood pressure, it might explain why some people have the condition despite a healthful lifestyle.

Gumz and her team want to determine if targeting Period 1 with a drug will effectively lower blood pressure in mice. The team’s initial experiments involving kidney cells and a commercially available drug indicate the strategy might work. The American Journal of Physiology, Renal Physiology published an article on the experiments in October.

They have applied for grants to continue their research in the hopes of finding a medication to help people with unexplained high blood pressure, sometimes called “essential hypertension.”

Jacob Richards, a Ph.D. student in the College of Medicine’s Interdisciplinary Program in Biomedical Sciences, joined Gumz’s laboratory in early 2011. He already has made his own significant contribution to the study of the body’s internal clocks, also known as circadian clocks or circadian rhythms.

Richards is the first author of the team’s paper about targeting Period 1 with a commercially available drug, published last month in the American Journal of Physiology, Renal Physiology, and of an overview article describing what’s known about the function of all of the body’s circadian clocks. Such a resource was lacking when Richards sought to educate himself on the subject after partnering with Gumz. The FASEB Journal, the Journal of the Federation of American Societies for Experimental Biology published the overview in September.

With so little known about the body’s circadian clocks, Gumz, Richards and their colleagues stand to make names for themselves as pioneers in studying the function of these important systems.

“This field is really just in its infancy, in terms of understanding the role of these clock proteins in blood pressure regulation,” Gumz said.