New technique to measure ATP from arterioles helps understand hypertension in women

Research at the University of Arkansas took a step toward understanding hypertension in women by using a new technique to examine the release of a neurotransmitter in small blood vessels.

After menopause, women have an increased risk of hypertension, and among older adults, more women than men have hypertension. Yet, research in hypertension has focused on males, and little is known about how women's bodies manage blood flow.

"The answer to why women have more problem with hypertension seems to be in the synapse," said exercise scientist Heidi Kluess.

Kluess explained that the synapse is the space between the nerve and the vascular smooth muscle, the place where the nerve and blood vessel interact. A neurotransmitter crosses the synapse to activate a receptor, which then causes the artery to constrict.

"There's been a little evidence to say that some of the neurotransmitter breakdown is different in women. It suggests that when we've been looking at receptors on the smooth muscle, we may have been missing a big part of the story, particularly in women," Kluess said. "That's where I started from."

Working with doctoral students Audrey J. Stone and Kirk W. Evanson, Kluess measured the neurotransmitter adenosine triphosphate (ATP) coming from the small blood vessels known as arterioles. ATP plays a key role in controlling blood flow and blood pressure by causing the diameter of blood vessels to change. Thus, the constriction of veins associated with hypertension could be related to relatively high levels of ATP in arterioles.

Kluess' first set of questions aimed at understanding where the ATP comes from, what tissues are releasing it and how this changes with aging.

According to Kluess, it was a challenge to work with the small blood vessels because they produce such a tiny amount of ATP and it was difficult to measure. To overcome this difficulty, the researchers used a new technique to measure ATP coming from the arterioles. A biosensor that was developed in the last few years uses a set of enzymes to indirectly measure ATP. Previously, the biosensor had been used only in research involving the brain. Kluess was the first to use the biosensor with vascular tissue.

"It's a great tool," Kluess said, "because it is in real-time and you get to see the ATP as it's released."

The research findings suggest that ATP from small arterioles can be measured and that the arteriole wall plays an important role in release and management of ATP. The researchers found that ATP is released mostly from the sympathetic nerves in the arteriole wall and that only a small part comes from the smooth muscle. Considerable research suggests that having a lot of ATP floating around in the blood vessels is not a good thing. The upside of this finding is that the nerve releases ATP in response to nerve signals. However, the mechanisms involved in the release of ATP by smooth muscles are less well understood, Kluess explained, and may result in chronically high ATP release.

The researchers found that the ATP overflow varied considerably with age. Because ATP is associated with vascular growth, it is important during early development when blood vessels are growing, but levels generally decline when people reach their twenties. Elevated levels can be a bad sign during aging when the body is no longer growing and may be a predictor of vascular changes that can be detected years before hypertension is a problem.

Some previous research had suggested that the endothelium - the outer layer of the smooth muscle - produced ATP. However, Kluess' research showed that the endothelial tissue did not produce ATP. Rather, it decreased levels of ATP and potentially plays a positive role in controlling ATP levels.

"That's an interesting finding because we know that as people age or develop disease that their endothelium doesn't work as well," Kluess said. "That may be a way that ATP increases during aging because the endothelium doesn't function as well and so can't buffer ATP quite as well."

More research is needed to investigate the factors that control ATP overflow and metabolism to reveal the mechanisms associated with age-related change. "We are very much at the beginning of this story," Kluess said.

Kluess is as assistant professor of kinesiology in the College of Education and Health Professions at the University of Arkansas. The article "ATP Overflow in Skeletal Muscle 1A Arterioles" was published online by the Journal of Physiology.