Nav: Home

With a broken circadian clock, even a low-salt diet can raise resting blood pressure, promote disease

February 01, 2016

AUGUSTA, Ga. - In the face of a disrupted circadian rhythm, a low-salt diet and a hormone known to constrict blood vessels have the same unhealthy result: elevated resting blood pressure and vascular disease, scientists report.

Sleep disorders, shift work, disease, even aging may be signs of or triggers for clock dysfunction that increases the risk for hypertension and blood vessel disease, and now scientists in the journal Hypertension show that even a low-salt diet can have an unfortunate synergy with a dysfunctional clock.

"Circadian rhythm is the daily rhythm in our bodies, and probably the most well-known is that of waking and sleeping," said Dr. Daniel Rudic, vascular biologist in the Department of Pharmacology and Toxicology at the Medical College of Georgia at Augusta University. While complex molecular networks actually regulate the rhythm, the daily cycle of daylight to dark resets the clocks, which plays a role in organ function throughout the body.

Sleep or rest time is when our 24-7 organs should get at least a bit of a break. It also appears to be a time circadian dysfunction can be silent and dangerous. "Blood flow to your organs is going to change when you are sleeping," Rudic said. "Your heart rate is going to decrease. One well-known observation is that the blood pressure exhibits a circadian rhythm." When resting blood pressures don't drop as they should, it's called nondipping.

"Our data suggests that low salt does what it should do in a normal mouse: it lowers blood pressure. But when we fed a low-salt diet to a mouse that had a circadian dysfunction, basically a sleep disorder, low sodium actually causes this nondipping blood pressure and vascular disease," Rudic said.

A low-salt diet is known in humans and animals to stimulate the renin-angiotensin-aldosterone system, which helps regulate blood pressure by prompting blood vessel constriction and holding onto fluids in the body. That system is the target of several existing blood pressure medications. While the why is not completely understood, low salt's triggering of the system may result from the body working to ensure an adequate blood pressure when there is so much less salt available, Rudic said. He notes that mice typically don't consume anywhere near the amount of salt most humans do and that he's not suggesting most of us abandon a low-salt diet.

Rather, while much work remains, the take-home message at this juncture is that in the ongoing struggle to control hypertension, which occurs in about half of patients, a 24-hour blood pressure check may reveal previously hidden nondipping and enable more targeted, effective treatment, he said.

In the studies, mice with one of their circadian rhythm genes, called Period isoform, knocked out had essentially the same blood pressure as mice with the gene. When Rudic's team gave the vasoconstrictor, angiotensin II, to the mice, not surprisingly, their blood pressure stopped the healthy dipping at rest and vascular disease accelerated.

On a low-salt diet, normal mice had the expected drop in blood pressure. However the Period isoform knockouts experienced the surprising nondipping blood pressure. In the case of the nocturnal mice, the dipping should have occurred during the daylight hours. Chronic consumption of a low-salt diet also caused their blood vessels to become narrowed and diseased. When scientists gave a drug that targets the renin-angiotensin-aldosterone system, it resolved the nondipping problems.

"Even though we can't currently directly target the circadian clock, clearly you can fix aspects of what the clock is influencing with antihypertensive medication," Rudic said. The optimal time of day for giving blood pressure medication to patients with signs of circadian clock dysfunction also needs further study, he said.

Unfortunately physicians today also can't directly look at their patient's clock function, although, again, sleep problems are a strong indicator and 24-hour blood pressure monitoring may help reveal nondipping blood pressure, Rudic said.

The scientists noted that the blood pressure in the normal and knockout mice was essentially normal without angiotensin or the low-salt diet, another surprise at least in the knockouts.

In humans, nondipping blood pressure is estimated as high as 45 percent and even higher - 53 percent - in patients being treated for hypertension.

In 2009, Rudic showed that in the blood vessels the circadian clocks regulate key signaling that enables them to dilate and remodel. He also reported in the journal Circulation that mice with mutated or missing clock genes were prone to vascular disease similar to smokers and people with high blood pressure and cholesterol.
-end-
The research was funded by the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Paramita Pati, a 2015 doctor of pharmacology graduate of Augusta University who is now a postdoctoral associate at Yale University, is the first author.

Augusta University generates national and global impact through groundbreaking research, patient-centered clinical expertise and forward-thinking educational programs from three campuses in the beautiful Southern city of Augusta, Georgia, and satellite locations across the state. Nearly 9,000 students choose Augusta for advanced health sciences and liberal arts education. Home to the state's only public academic medical center, Augusta's world-class clinicians are bringing the medicine of tomorrow to patient care today.

Medical College of Georgia at Augusta University

Related Blood Pressure Articles:

Do you really have high blood pressure?
A study by researchers at the University of Montreal Hospital Research Centre (CRCHUM) shows that more than half of family doctors in Canada are still using manual devices to measure blood pressure, a dated technology that often leads to misdiagnosis.
Why do we develop high blood pressure?
Abnormally high blood pressure, or hypertension, may be related to changes in brain activity and blood flow early in life.
For some, high blood pressure associated with better survival
Patients with both type 2 diabetes and acute heart failure face a significantly lower risk of death but a higher risk of heart failure-related hospitalizations if they had high systolic blood pressure on discharge from the hospital compared to those with normal blood pressure, according to a study scheduled for presentation at the American College of Cardiology's 66th Annual Scientific Session.
$9.4 million grant helps scientists explore how cell death from high blood pressure fuels even higher pressure
It's been known for decades that a bacterial infection can raise your blood pressure short term, but now scientists are putting together the pieces of how our own dying cells can fuel chronically high, destructive pressure.
Blood pressure diet improves gout blood marker
A diet rich in fruits, vegetables, low-fat dairy and reduced in fats and saturated fats (the DASH diet), designed decades ago to reduce high blood pressure, also appears to significantly lower uric acid, the causative agent of gout.
New tool to improve blood pressure measurement
Oxford University researchers have developed a prediction model that uses three separate blood pressure readings taken in a single consultation and basic patient characteristics to give an adjusted blood pressure reading that is significantly more accurate than existing models for identifying hypertension.
Blood vessels sprout under pressure
It is blood pressure that drives the opening of small capillaries during angiogenesis.
Better blood pressure control -- by mobile phone
An interactive web system with the help of your mobile phone can be an effective tool for better blood pressure control.
Time to reassess blood-pressure goals
High blood pressure or hypertension is a major health problem that affects more than 70 million people in the US, and over one billion worldwide.
With help from pharmacists, better blood pressure costs $22
A pharmacist-physician collaboration in primary-care offices effectively and inexpensively improved patients' high blood pressure.

Related Blood Pressure Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...