Our kidneys filter 180 liters of fluid and a pound of salt each day to keep blood pressure levels in balance. They are the unsung heroes in maintaining healthy blood pressure.

But as it turns out, a cellular pathway outside the kidneys is performing some of the heavy liftings when it comes to maintaining blood pressure control, according to new research from geneticists and nephrologists at the University of Pittsburgh.

The study, which was published today in the American Heart Association journal Hypertension, suggests a possible new target for clinical studies to examine the potential blood pressure-lowering effects of current drugs.

“Our findings were entirely unexpected,” remarks Brandon Michael Blobner. “Previously there had been some hints that mutations to salt-processing channels outside the kidneys affected blood pressure, but it would have been impossible to confirm the mechanism without the massive genetics databases that we had access to through cross-disciplinary partnerships.” 

Hypertension, or high blood pressure, affects nearly half of U.S. adults. It is linked to chronic kidney disease and stroke, and it affects Black people more than other groups.

According to the US Centers for Disease Control and Prevention, only 1 in 4 persons have high blood pressure under control, making it one of the largest public health issues in the country.

The imbalance in fluid and salt levels, which strains artery walls and harms blood vessels and organs, contributes to high blood pressure.

The Pitt study concentrated on the channels or passages that particular cell membranes utilize to control fluid volume based on how much sodium the cells possess.

Blobner wondered if changes in the genes that encode the channel’s subunits would have an impact on blood pressure.

Blobner and Ryan Minster, Ph.D., assistant professor of human genetics at Pitt’s School of Public Health, built a dataset with genomic sequences and blood pressure records on more than 28,000 people who were taking part in either the Trans-Omics in Precision Medicine (TOPMed) Whole-Genome Sequencing Project or the Somoan Soifua Manuia Study with the support of Thomas Kleyman, M.D., the Sheldon Adler Professor of Medicine at

For Minster, “one of the really exciting things” about the project was “that it was so targeted and hypothesis-driven”. 

“Often with these big genomics projects, we’re more agnostic – casting a wide net – and it can take decades for validation of a discovery. This project made a significant find remarkably quickly.” 

The alpha, beta, and gamma subunits of the channel are all located in kidney cells, and scientists have long known that uncommon abnormalities in these genes might result in dangerously high blood pressure.

However, when researchers focused on more modest alterations, they found that a fourth component called delta affects blood pressure. It is significant that immune cells, as well as those that border the lungs, heart, and colon, include delta.

“I’m a nephrologist – my entire career has been dedicated to understanding the kidney and its role in maintaining sodium levels to moderate blood pressure,” adds Kleyman. “But our research in the last several years has expanded my focus. This study cements that we must branch beyond the kidney to better target blood pressure medications.” 

One of the risks associated with several blood pressure drugs is the potential for fatally high potassium levels. However, this issue is linked to dysfunctional kidneys.

Theoretically, such drugs may be an effective treatment with a lower risk of excessive potassium levels if a person’s high blood pressure is caused by fluid and salt imbalances brought on by broken channels in cells beyond the kidneys.

“One of the things we’re particularly interested in at UPMC is targeting therapeutics – you want to give the right drug to the right person at the right time,” Kleyman adds. “This study may help us someday identify people with specific, subtle genetic mutations that predispose them to a type of hypertension acting outside the kidneys. Knowing that, we can better help that person control their blood pressure.”

Image Credit: Getty

You were reading: A New Drug Target To Keep Blood Pressure Under Control: “Entirely Unexpected”