Let’s face it: salt is delicious. But when it comes to diet and high blood pressure, salt has long been one of the bad guys. Too much sodium can make your body retain water, increasing pressure within blood vessels and leading to hypertension. And runaway blood pressure can lead to a host of maladies, from kidney damage and vision loss to stroke and heart disease.

Most Americans do eat too much salt—3.5 grams each day, more than 7 times what we need, according to the US Centers for Disease Control and Prevention. But the extra salt doesn’t affect everyone equally. According to Richard Wainford, a School of Medicine assistant professor of pharmacology and medicine, only about half of adults are salt-sensitive: if they eat too much salt, their blood pressure goes up. For the other half, salt has little or no effect on blood pressure. Nobody knows exactly why, and there’s no easy way to tell who’s who.

“Something has got to be working in your body to get rid of that salt,” says Wainford, who heads a laboratory at MED’s Whitaker Cardiovascular Institute. “We don’t know what that is. So if we don’t know what’s working in a healthy patient, how can we expect to fix something when it’s broken? That’s where I come in.”

Wainford specializes in the complex science of homeostasis—how the body maintains a stable balance of substances like sodium, glucose, and iron throughout its tissues—and its impact on blood pressure regulation. His research is funded by two grants from the National Institutes of Health’s National Heart, Lung, and Blood Institute and his goal is to develop biomarkers for salt-sensitivity, which could lead to better diagnostics and treatment for high blood pressure.

One of the key organs for homeostasis is the kidney, which helps regulate water, salt, and iron in the blood by excreting certain substances in the urine. Another key organ is the brain, which helps control the kidneys. Wainford studies the kidney-brain conversation by examining a particular signaling pathway in the brain, one that sends messages through certain molecules, known as Gαi₂-proteins.

When a person ingests salt, signals along this pathway tell the brain to slow down communication to the kidney, and also for the kidney to increase the amount of salt in urine. It’s a complicated chain of events, and Wainford studies how it works in rats.

In one of his first experiments, Wainford worked with several breeds of salt-resistant rats, animals that can eat as much salt as they want with no effect on blood pressure. After feeding them salty diets for three weeks, he looked at the expression of the Gαi₂-proteins in their brains, and found a dramatic increase in a region of the brain known to be a “hot spot” for cardiovascular regulation. Wainford then blocked the signal pathway by infusing the rats with a specific sequence of DNA that prevented them from making the Gαi₂-protein. Then he gave the animals salty food again, but this time, they couldn’t get rid of the extra salt. As a result, they got high blood pressure.

“When healthy people eat salt, the activity of their central nervous system is turned down to get rid of it,” says Wainford. “When you remove this protein pathway in the brain of salt-resistant rats, they’re not able to turn down the activity of the brain to the same extent.” He believes this signaling pathway is one of several that affect the control of blood pressure. Other studies in humans have shown that a tiny defect in the gene for this protein—one single base pair off—is linked to hypertension. But Wainford’s group is the first to find how it works: a clear molecular mechanism that regulates the communication between the brain and the kidney.

Wainford did similar tests on salt-sensitive rats, and with a more drastic measure of removing the animals’ renal nerves entirely, severing all communication between the brain and the kidneys. Surprisingly, this kept the rats’ blood pressure low and seemed to have no other ill effects. (Similar trials on humans have had mixed results.)

“Clearly the impact of the renal nerves on blood pressure regulation in human subjects is complicated,” says Wainford. “I think the removal of the renal nerves is a very powerful technique; it just needs to be done right, and studied right, and in the right population. Ultimately, our goal is to more fully understand the mechanisms of how the brain and the kidney interact to regulate blood pressure. The more we understand that, the better we can treat patients.”

This story was originally published on BU Research.