A Colorado State University researcher has teamed up with the Mayo Clinic to pin down what causes blood vessels to expand and contract during exercise.
Findings from the $3 million project funded by the National Institutes of Health could uncover new treatment options for diabetes, strokes and heart attacks.
Frank Dinenno, director of CSU’s Human Cardiovascular Physiology Laboratory, is a principal investigator on the study. It looks at the role of adenosine triphosphate, or ATP, a chemical that can be released by red blood cells and is believed to cause blood vessels to dilate during exercise, when muscles demand more oxygen.
“The general hypothesis is that as you raise oxygen, there should be less ATP and lower tissue blood flow,” Dinenno said. “When you lower oxygen, there should be more ATP and greater tissue blood flow.”
The four-year project, funded by the National Heart, Lung and Blood Institute (NHLBI) at the NIH, will be conducted with Michael Joyner of the Mayo Clinic in Minnesota. Dinenno said the Mayo Clinic is an important partner because it has one of the only hyperbaric chambers in the world that supports invasive studies in humans. This allows researchers to increase the level of oxygen in subjects’ blood while simultaneously monitoring bodily changes.
The Mayo Clinic also sees a significant number of cystic fibrosis patients who, along with older adults, will be key test subjects because their ATP levels remain unchanged during exercise, while the levels of the chemical can double in young, healthy individuals, who are also part of the study.
In the study, titled “Exercise hyperemia in humans,” the researchers will manipulate oxygen levels in the blood with and without exercise in subjects from all three groups, in an effort to stimulate the release of ATP into circulation.
The CSU lab was the first to show that red blood cells in older adults don’t release more ATP during exercise or when their isolated red blood cells are exposed to low oxygen.
In this next step, Dinenno says, he and Joyner are hoping to support the theory that ATP is indeed an important chemical that signals the vessels to expand when and where more oxygen is needed. They expect to demonstrate that as more oxygen is introduced into the blood, there is less ATP released by red blood cells, and when oxygen is lowered, ATP release is increased.
In the cystic fibrosis patients and older adults, there are several possible outcomes when oxygen levels in the blood are manipulated. First, their bodies could respond normally, with ATP and blood flow both increasing at lowered oxygen levels, which Dinenno said is unlikely given pilot data generated for the proposal. Second, ATP might respond normally under extremely high- or low-oxygen conditions but blood flow does not. Or third, their blood flow might rise and fall in response to the fluctuating oxygen levels without any change in ATP, which would be counter to their theory that ATP causes the dilation.
If researchers can show that ATP does stimulate blood vessels to relax and increase blood flow and oxygen delivery, it could pave the way for new drugs that stimulate ATP release from red blood cells, which could have broad clinical applications. For example, ATP release is impaired in diabetics, and when specific tissues don’t get enough blood it can cause events like strokes and heart attacks.
Dinenno, who used much of the grant he received as a CSU Monfort Professor to fund the data-gathering that helped land him and Joyner the NIH grant, said their project will also involve extracting red blood cells and manipulating their oxygen levels to isolate ATP.
Testing that doesn’t require the hyperbaric chamber, such as monitoring subjects as they exercise with and without low oxygen and isolating red blood cells from healthy young and older adults, will be conducted at the CSU lab. The project will involve about 160 young people, approximately 70 older adults and about 40 cystic fibrosis patients.
“This recent award from the NIH is another example of Dr. Dinenno’s commitment to addressing questions rooted in basic physiology that also have clear real-world clinical applications,” said Barry Braun, head of the Department of Health and Exercise Science.