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UVA School of Medicine scientists have obtained important new insights into how our bodies regulate our blood pressure by revealing how our cells turn off a key hormone. The findings could open the door to new treatments for hypertension (high blood pressure) and kidney diseases, the researchers report.

The findings, from UVA’s R. Ariel Gomez, MD, and Maria Luisa S. Sequeira-Lopez, MD, shed light on how specialized kidney cells, called juxtaglomerular cells, shut down the production of renin, a hormone released to increase blood pressure. Excessive production of the hormone can cause hypertension. 

“Studying the intricate communication system within the cells that produce the hormone renin is a fundamental first step to understand high blood pressure,” says Dr. Sequeira-Lopez, UVA Child Health Research Center. “Grasping how calcium behaves in juxtaglomerular cells may help create new and safer treatments for heart, vascular, and kidney diseases.” 

Better Understanding Blood Pressure Control

Juxtaglomerular cells act as the body’s blood pressure sensor. They prevent our blood pressure from dropping too low by releasing renin as needed. To determine this, they monitor calcium levels within themselves. In that sense, calcium is the on-off switch for renin production.

The mechanism that stops renin production, however, has been poorly understood. UVA’s new research shows the hormone angiotensin II (often called ang II) causes calcium levels within the cells to rise and fall in bursts. These “oscillations” ultimately suppress renin release, the scientists determined.

While earlier studies had looked at renin production in single cells, UVA’s new research reveals how the process works in actual kidney tissue. The scientists found, for example, that a calcium surge doesn’t stay in just one cell. Instead, it spreads through neighboring juxtaglomerular cells to slow renin production more effectively.

The scientists found that looking at isolated cells was a poor way to understand the complex cellular interactions responsible for halting renin production and release to the bloodstream. Their work, examining living kidney tissue, has produced a far more holistic understanding of renin regulation and the mechanisms that control it.

“When observed in intact kidney tissue, calcium signals in juxtaglomerular cells show more dynamic and refined patterns than those typically observed in isolated cells," says postdoctoral researcher Hiroki Yamaguchi, MD, PhD, the first author of a scientific paper detailing the findings. “We see these calcium signals as transducers that coordinate hormonal, pressure, and neural cues to finely tune renin release. We are eager to explore this mechanism further.”

The new insights into how our bodies control renin production and, in turn, our blood pressure could pave the way for new ways to reduce high blood pressure and the complications it can cause, the researchers say.

“Research into calcium signaling in juxtaglomerular cells may lead to the development of novel and safer drugs to control blood pressure more precisely,” says Dr. Gomez, Director, UVA Child Health Research Center. “Traditionally, we have concentrated our attention on what turns hormones and systems on. Focusing on the regulatory brakes, the ‘off switches’ of hormone production, offers a novel opportunity to understand and maintain well-being.”

Findings Published

UVA’s findings have been detailed in the scientific journal Circulation Research. The article is free to read. 

The research team consisted of Yamaguchi, Nick A. Guagliardo, Laura A. Bell, Manako Yamaguchi, Daisuke Matsuoka, Fang Xu, Jason P. Smith, Mohamed Diagne, Sophie Condron, Lucas F. Almeida, Silvia Medrano, Paula Q. Barrett, Edward H. Nieh, Dr. Gomez, and Dr. Sequeira-Lopez. 

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