Penn Dental Medicine Study Finds Unexpected Side Effects with Commonly Prescribed High Blood Pressure Medications

PHILADELPHIA, April 22, 2025 /PRNewswire/ -- High blood pressure, or hypertension, affects more than 1 billion people globally. Many of them are prescribed angiotensin-converting enzyme inhibitors—better known as ACE-1 inhibitors (ACEIs)—and/or angiotensin receptor blockers (ARBs), which act on the renin-angiotensin (RAS) pathway. But hypertension remains uncontrolled in most people with the disease, indicating that other affordable treatments are needed.

Now, in a study published in Hypertension Research, researchers at Penn Dental Medicine and Penn Medicine have investigated the benefits of adding oral ACE2—previously shown to have positive effects in injectable form for RAS-associated metabolic diseases—to these commonly prescribed medications.

"This enzyme [ACE2] also regulates hypertension and heart disease," notes Henry Daniell, W.D. Miller Professor at Penn Dental Medicine. Yet, he says, no one had looked at the relationship between these drugs and ACE2.

The RAS pathway regulates blood pressure by triggering the release of renin when blood pressure falls. Renin converts angiotensinogen into angiotensin I, which ACE then converts into angiotensin II, a vasoconstrictor. ACE inhibitors and ARBs lower blood pressure by acting on different steps of this process: ACE inhibitors inhibit the formation of angiotensin II, while ARBs block its ability to bind to its receptors. ACE2 lowers angiotensin II levels by converting it to angiotensin1-7 (Ang1-7), which promotes vasodilation and reduces blood pressure.

In this study, Daniell and colleagues built on their previous work using a lettuce-based plant-encapsulated system to evaluate oral delivery of ACE2 in dogs with myxomatous mitral valve disease. Importantly, these dogs also had elevated systolic blood pressure that was being treated with ACEIs and/or ARBs.

What they found surprised them. "The first surprise," says Daniell, "was that in the dogs on ACE inhibitors, those drugs inhibited the enzyme [ACE2] that we were giving them." And the second surprise? ARBs increased the angiotensin II pool. Daniell notes these are two things you don't want to do when trying to lower blood pressure. The good news, he says, is that not all ACEI drugs inhibited ACE2 activities equally.

Next steps are to repeat this study with dogs on lisinopril. Daniell explains, "We did this study to see how beneficial ACE2 is, but we couldn't do that because its activity was killed by all ACE inhibitors except for lisinopril." Ultimately, Daniell would like to use his plant-encapsulation system to evaluate the benefits of ACE2 treatment in humans. Read more>>

Contact: Beth Adams, [email protected]

SOURCE PENN DENTAL MEDICINE