Baroreceptors — natural blood-pressure barometers inside our bodies — detect subtle changes in blood pressure and adjust hormone levels to keep it in check. Scientists have long suspected that these pressure sensors existed in specialized kidney cells called renin cells, but no one has been able to locate them until now.
Watanabe et al. show that the enigmatic baroreceptor is a nuclear mechanotransducer that resides in the renin cells per se and is responsible for the sensing and transmission of extracellular physical forces directly to the chromatin of renin cells via lamin A/C to regulate renin gene expression, renin bioavailability, and homeostasis. Image credit: Watanabe et al., doi: 10.1161/CIRCRESAHA.120.318711.
In 1957, Dr. Louis Tobian from the University of Minnesota School of Medicine and his colleagues proposed the existence of a pressure sensor inside renin cells.
It made sense: the cells had to know when to release renin, a hormone that helps regulate blood pressure.
But even though scientists suspected this cellular barometer had to exist, they couldn’t tell what it was and whether it was located in renin cells or surrounding cells.
“Renin-expressing cells are essential for survival, perfected throughout evolution to maintain blood pressure and fluid-electrolyte homeostasis,” explained Dr. Maria Luisa Sequeira-Lopez from the University of Virginia School of Medicine and her colleagues.
“In adult mammals, renin cells are strategically located at the juxtaglomerular tip of the afferent arterioles as they enter the glomeruli.”
“Renin cells are sensors endowed with the ability to detect and respond to minute changes in blood pressure and the composition and volume of the extracellular fluid.”
“In response to a decrease in perfusion pressure, renin cells synthesize and release renin to the circulation resulting in the restoration of blood pressure.”
“An increase in pressure, on the other hand, results in decreased renin release, thus preventing the development of hypertension.”
“How renin cells sense and respond to changes in pressure is unknown.”
Using a variety of novel in vivo and in vitro approaches, the researchers determined that the baroreceptor was a mechanotransducer inside renin cells.
This mechanotransducer detects pressure changes outside the cell, then transmits these mechanical signals to the cell nucleus, like how the cochlea in our ear turns sound vibrations into nerve impulses our brain can understand.
The scientists found that applying pressure to renin cells in lab dishes triggered changes within the cells and decreased activity of the renin gene, Ren1.
They also compared differences in gene activity in kidneys exposed to lower pressure and those exposed to higher pressure.
Ultimately, when the baroreceptors detect too much pressure outside the renin cell, production of renin is restricted, while blood pressure that is too low prompts the production of more renin.
This marvelous mechanism is vital to the body’s ability to maintain the correct blood pressure.
“It was exhilarating to find that the elusive pressure-sensing mechanism, the baroreceptor, was intrinsic to the renin cell, which has the ability to sense and react, both within the same cell,” Dr. Sequeira-Lopez said.
“So the renin cells are sensors and responders.”
The findings appear in the journal Circulation Research.
Hirofumi Watanabe et al. 2021. Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis. Circulation Research 129: 262-276; doi: 10.1161/CIRCRESAHA.120.318711