For more than seventy years, a drug called hydralazine has been used around the world to treat high blood pressure.
It is one of the oldest medicines of its kind and is especially important for treating preeclampsia, a dangerous condition that can affect pregnant women. Even though doctors have relied on this drug for generations, they never actually knew how it worked inside the body.
Hydralazine was created long before modern tools allowed scientists to study how medicines act at the molecular level. It simply worked, and that seemed to be enough.
Now, a team of researchers from the University of Pennsylvania has finally solved this mystery. What they discovered is surprising and could open the door to a completely new use for hydralazine: stopping the growth of aggressive brain tumors.
Preeclampsia is a condition that causes very high blood pressure during pregnancy and puts both the mother and baby at risk. It can be deadly if not treated quickly.
Hydralazine has long been one of the standard medicines used to bring down dangerously high blood pressure in these emergencies. According to the researchers, this medicine has saved countless lives over the past several decades, especially in places where other treatments are not easily available.
But even with all of its success, scientists never fully understood what hydralazine did at the microscopic level.
Dr. Kyosuke Shishikura, one of the lead scientists on the new study, explains that the drug belonged to a period of medicine when doctors would discover chemicals through trial and error before they understood why they worked. This left many unanswered questions about safety and possible new uses.
In their new study, published in Science Advances, the team discovered that hydralazine works by blocking a special enzyme called ADO, short for 2‑aminoethanethiol dioxygenase. This enzyme acts like a tiny oxygen alarm system inside the body.
When oxygen levels fall, ADO quickly sends out a signal that makes blood vessels tighten. This tightening raises blood pressure so that the body can keep supplying oxygen to important organs.
Hydralazine binds to ADO and shuts off this alarm system. When the alarm stops ringing, the blood vessels stop tightening. Proteins inside the cells called RGS proteins begin to build up, and these proteins send a message telling the blood vessels to relax.
As the muscles inside the blood vessel walls loosen, blood pressure drops. This finally explains why hydralazine has been such an effective medicine for high blood pressure for so many years.
But the most surprising part of the research came when the scientists realized that the same oxygen‑sensing pathway is also used by certain brain tumors to survive. Glioblastoma, one of the most aggressive and deadly forms of brain cancer, often grows in parts of the brain where oxygen is very low.
Tumor cells need ADO to help them stay alive in these harsh conditions. Researchers already suspected that ADO played a role in helping these tumors spread, but until now, they did not have a drug that could block it.
When the Penn team and their collaborators tested hydralazine on brain cancer cells, they made an important discovery. Instead of killing the cells outright, the drug forced them into a resting state known as senescence.
In this state, the cells stop growing and dividing. This is important because it avoids some of the problems caused by traditional chemotherapy, such as severe inflammation or the tumor becoming resistant to treatment. Hydralazine essentially pushed the tumor cells into a deep sleep.
These results were strengthened through collaboration with structural biochemists from the University of Texas, who used a method called X‑ray crystallography to show exactly how hydralazine attaches to the ADO enzyme. Neuroscientists at the University of Florida then tested the drug’s effects on real brain cancer cells and confirmed what the Penn team suspected.
The next challenge for the researchers is to design new medicines that target ADO even more precisely. Hydralazine works, but it was not originally made for cancer treatment, and it does not easily cross into the brain. The team hopes to create new versions of the drug that reach brain tumors more effectively and avoid affecting healthy tissues.
This new understanding of hydralazine also gives scientists hope for better treatments for preeclampsia. Because the drug’s exact mechanism is now clear, researchers can begin designing safer and more selective medicines for pregnant women who need blood pressure control.
When we look closely at this study, the findings are extremely meaningful. First, the researchers solved a decades‑old mystery about how a common medicine works. Second, they found an unexpected connection between high‑blood‑pressure disorders and brain cancer.
Third, they showed that an old drug may have new life as a treatment for one of the deadliest cancers known. These discoveries help remind us that some answers have been hiding in plain sight for decades, inside medicines we already use every day.
If you care about blood pressure, please read studies about unhealthy habits that could increase high blood pressure risk, and eating eggs in a healthy diet may reduce risks of diabetes, high blood pressure.
For more information about blood pressure, please see recent studies that early time-restricted eating could help improve blood pressure, and results showing 12 foods that lower blood pressure.
The study is published in Science Advances.
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