Hypertension in the lungs is a relatively rare but very serious disease that is usually fatal within two years if left untreated. Current therapies can slow down its progression, but no cure exists. Research teams from Bochum and Bonn are shedding light on the underlying mechanisms of the disease, and have discovered a previously unrecognized factor in its development: the protein beta arrestin 1. The teams have shown that this protein plays an important role in transporting signaling molecules involved in regulating blood vessel diameter. The researchers report their findings in the journal Proceedings of the National Academy of Sciences (PNAS) from February 9, 2026.

Narrowing of the blood vessels in the lung is the most important cause of pulmonary hypertension, as narrowed vessels reduce the space available for blood flow, causing pressure to rise. The acute regulation of vessel diameter works like this: Endothelial cells lining the blood vessels release nitric oxide (NO). NO diffuses into the surrounding smooth muscle cells and activates soluble guanylate cyclase (sGC). This in turn aids in the formation of cGMP, which leads to the relaxation of the muscle cells, by reducing intracellular calcium concentration.

“At first glance, the beta arrestin protein has nothing to do with these processes,” says Professor Daniela Wenzel, Chair of the Department of Systems Physiology at Ruhr University Bochum. The protein, which exists in variants 1 and 2, is known for inhibiting G proteins. “But beta arrestin can do much more,” says Wenzel. “It is also a scaffold protein that connects to other signaling molecules and helps guide them to where they need to be in the cell.”

The researchers from Bochum and Bonn wanted to know whether beta arrestin also plays a role in vessel diameter regulation. To find out, they conducted various experiments with genetically modified mice lacking a specific beta arrestin subtype. Do their lung vessels respond to the relaxation factor NO similarly to those of unmodified wild-type mice?

The result: Mice without beta arrestin 2 do not differ from the wild type. In contrast, mice without beta arrestin 1 have pulmonary hypertension. Upon NO administration, their lung vessels did not dilate to the same extent as those in the other groups.

“It is clear that beta arrestin 1 is involved in the development of pulmonary hypertension,” concludes Dr. Alexander Seidinger, one of the study’s first authors. “And, of course, we wanted to know the underlying mechanism.” Further experiments showed that the key lies in the activity of the soluble guanylate cyclase. Its activation requires a heme with an iron molecule at the center. This iron molecule must be in a divalent state for the mechanism to function.
“We were able to demonstrate that beta arrestin 1 physically binds to soluble guanylate cyclase,” reports Seidinger. Other experiments revealed that beta arrestin 1 helps transport an enzyme to the heme of the soluble guanylate cyclase. That enzyme reduces the heme if it is oxidized. “This resensitizes the guanylate cyclase to NO,” Seidinger explains.

“This discovery opens up a lot of questions,” says Professor Bernd Fleischmann, Chair of the Institute of Physiology I at Bonn University and University Hospital Bonn. Could there be a genetic mutation in patients with pulmonary hypertension that affects beta arrestin 1? “In the future, we might be able to develop an activator for beta arrestin 1 potentially leading to more effective treatments for pulmonary hypertension.”