Study isolates target for hypertension treatment
Researchers at the Brody School of Medicine at ECU have identified a receptor in the human brain that could lead to more effective treatments for high blood pressure.
The receptor is B1R, which plays a significant role in inflammation, pain signaling and immune response. B1R has garnered attention in recent years due to its involvement in various diseases, including neuropathic pain, cardiovascular disorders and cancer — and now, potentially, hypertension — and is emerging as a potential therapeutic target for drug development.
“We’ve uncovered a new pathway that we can potentially target to better control this widespread and dangerous condition,” said Srinivas Sriramula, an associate professor of pharmacology and toxicology whose lab led the study. “It validates years of research effort and collaboration among different laboratories.”
The team published its study, “Targeting Kinin B1R Attenuates Hypertension Through AT1R-Dependent Mechanisms,” in August in Circulation Research, the journal of the American Heart Association. The study was funded by a five-year, $1.8 million grant from the National Heart, Lung and Blood Institute.
Heart disease is the leading cause of death in the U.S., according to the federal Centers for Disease Control and Prevention. Stroke is No. 4, and high blood pressure, or hypertension, is a leading risk factor for both. In North Carolina, more than 1 in 3 adults have it, and not all cases respond adequately to lifestyle changes and medication.
Sympathoexcitation, or the activation or stimulation of the sympathetic nervous system, which is responsible for the body’s “fight or flight” response, can lead to increased heart rate and blood pressure. It has been associated with increased B1R activation in the brain.
The lab previously identified a relationship between angiotensin II stimulation and B1R expression. The angiotensin II hormone plays a role in regulating blood pressure by constricting blood vessels and increasing blood volume.
So the research team went to work figuring out how B1R might be modulated in an overactive nervous system, contributing to high blood pressure. They blocked B1R from expressing itself in laboratory models and, in so doing, reduced high blood pressure and associated inflammation. They then studied postmortem brains from hypertensive human patients and found B1R was overexpressed.
“We discovered for the first time that the kinin B1 receptor interacts with the angiotensin II type 1 receptor, which is a major target for current antihypertensive drugs,” Sriramula said. “This interaction opens up the possibility that B1R could serve as a new therapeutic target.”
Doctoral student Drew Theobald and Riley Bessetti ’25 are the first and second authors of the paper.
“People take medications but still don’t reach healthy blood pressure levels. Finding new pathways that drive hypertension could offer insights to new targets to help those patients achieve better control,” Theobald said.
Other study authors are Karen Litwa of the Brody School of Medicine, Yumei Feng at the University of Rochester Medical Center in New York and Eric Lazartigues at the Louisiana State University Health Sciences Center in New Orleans.