UToledo Receives More Than $3.8 Million for Novel Hypertension Research

UToledo Receives More Than $3.8 Million for Novel Hypertension Research

The drug market is awash with hypertension medications, but even with dozens of options available some people find it difficult getting their blood pressure under control.

Researchers at The University of Toledo believe one solution to overcoming uncontrolled hypertension may come from a seemingly unlikely target: the gut.

"There is unquestionably a link between what happens in our gut and how well our blood pressure is regulated," said Dr. Bina Joe, Distinguished University Professor and chair of the UToledo Department of Physiology and Pharmacology. "As we dig deeper and learn more, we are getting closer to the potential of totally new methods for treating hypertension."

Joe recently received a five-year, $3.85 million grant from the National Heart Lung and Blood Institute to investigate how bacteria-driven changes to bile acids in the gut affect blood pressure.

A pioneer in the field of hypertension research, Joe's lab previously found that lower levels of conjugated bile acids correlated with higher blood pressure readings in both animal models and humans.

Bile acids are produced in the liver and delivered to the gut, where they play an important role in digestion. Bile acids are naturally conjugated - or joined - with the amino acids taurine and glycine when they are released to the gut.

In a study published last year in the Journal of Hypertension, Joe's lab detailed how bacteria can rearrange the chemical structure of those conjugated bile acids in the gut, changing them to unconjugated bile acids.

Not only did the research show that more unconjugated bile acid was predictive of hypertension, but it also found higher populations of a particular bacterium in hypertensive test subjects that is known to deconjugate bile acids.

By feeding hypertensive animal models taurine or taurocholic acid supplements, Joe's team was able to increase the amount of conjugated bile acid in their gut and in turn reduce their blood pressure.

The new NIH-supported research seeks to build on those earlier findings.

"The overarching hypothesis of this proposal is that conjugated bile acids are novel antihypertensive metabolites," Joe said. "Our research will focus on uncovering why conjugated bile acids depleted in hypertension and identifying the mechanism by which those conjugated bile acids protect against hypertension."

Working with a special line of germ-free animal models that completely lack microbiota, Joe and her team will be able to zero in on the role specific gut bacteria play in depleting or enhancing the conjugated bile acids.

UToledo researchers also will study the specific pathways by which taurocholic acid lowers hypertension. That knowledge, Joe said, is critical before using taurine/taurocholic acid as potential treatment for hypertension can be advanced beyond animal studies.

If that treatment were to move forward, it would be the first anti-hypertensive medication that targets the gut-liver axis.

There are several classes of available blood pressure medications, but in general they target the brain, heart or kidneys to prevent blood vessels from narrowing, lower the heart rate or remove excess water and sodium from the body.

"Despite all of the available medications, the prevalence of hypertension is on the rise and treatment-resistant hypertension remains a real issue," Joe said.

Nearly half of U.S. adults have hypertension, now defined as blood pressure at or above 130/80. Of those being treated for hypertension, between 10% and 20% did not have their blood pressure under control despite aggressive measures.

"We at The University of Toledo are attacking this problem with a new thought," Joe said. "The gut and the bacteria that call it home are targets that science has missed in the past. This is an exciting area of research and we are at the forefront of it."