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Common High Blood Pressure Meds May Have Unexpected Side Effects, Penn Study Finds
PHILADELPHIA (Archyde.com) — Widely prescribed medications for high blood pressure,including some angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (arbs),may have previously unrecognized effects on a critical enzyme that regulates blood pressure and plays a role in COVID-19,according to a new study from the University of Pennsylvania School of Dental medicine. Cardiovascular diseases remain the world’s leading cause of death, including in the United States, and hypertension affects more than a billion people worldwide.
The research,published in Hypertension Research,focuses on the renin-angiotensin (RAS) pathway,a key regulator of blood pressure. Many individuals diagnosed with hypertension are prescribed ACE inhibitors and/or ARBs, which target this pathway. Though, hypertension remains uncontrolled in many patients, highlighting the need for additional treatment options.
Dr. Henry Daniell, W.D. Miller Professor at Penn’s School of Dental Medicine and a co-author of the study,said that while the RAS pathway and the related ACE2 enzyme are known to regulate hypertension and heart disease,“no one had looked at the relationship between thes drugs and ACE2.”
The RAS pathway increases blood pressure by prompting 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 work at different steps in this process. ACE inhibitors inhibit the creation of angiotensin II,while ARBs block angiotensin II’s ability to bind to its receptors. ACE2, conversely, lowers angiotensin II levels by converting it to angiotensin 1-7 (Ang1-7), which promotes vasodilation and reduces blood pressure.
The study, performed on pet dogs already taking medication for heart conditions, yielded unexpected results. As the animals were pets, “the owners, understandably, did not wont to change their current medications. so, we had to continue their treatments with ACEI or ARB and then give them ACE2 along with see whether it was beneficial,” daniell explained.
The researchers found that certain ACE inhibitors inhibited the ACE2 enzyme,while ARBs increased the angiotensin II pool.
“The first surprise,” said Daniell, “was that in the dogs on ACE inhibitors, those drugs inhibited the enzyme [ACE2] that we were giving them.” The second surprise? ARBs increased the angiotensin II pool.
Daniell emphasized the potential negative impact of these findings. “You don’t want to inhibit ACE2, and you don’t want to increase the angiotensin II pool. And here we saw both.” However, the study also revealed that not all ACEI drugs are created equal. Lisinopril,a widely prescribed ACE inhibitor in the United States,inhibited ACE2 much less than other ACEI drugs.
The findings have important clinical relevance for human patients, as many are prescribed one or both of these medications. ACE2, the study suggests, has cardioprotective effects that may have therapeutic potential.Moreoever, ACE2 inhibition has been linked to SARS-CoV-2, the virus that causes COVID.
“I was stunned because this inhibition [with ACE inhibitors] was just like what we observed with the coronavirus,” daniell said. “Given what we saw during the pandemic, there is no question that ACE2 is a key metabolic enzyme.”
Looking ahead, Daniell and his team plan to repeat the study using only dogs on lisinopril. “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,” he said.
Daniell is also eager to evaluate the benefits of ACE2 treatment in humans using his plant encapsulation system, which has recently received FDA Investigational New Drug (IND) approval. This approval makes “ACE2 the first engineered human blood protein expressed in plant cells approved by the FDA for evaluation in human clinical trials.” Currently, there is no biologic drug to improve cardiopulmonary diseases.
“The average cost of launching a new injectable biologic drug [like ACE2] is $2.5 billion,” said Daniell. “My entire career has been focused on making drugs affordable—especially for common diseases like diabetes and hypertension.”
Counterargument and Rebuttal
one potential counterargument is that the study was conducted on dogs, and the results may not directly translate to humans. While this is a valid point, the RAS pathway is highly conserved across species, and canine models are frequently used in cardiovascular research. Furthermore, the study highlights a potential mechanism of action that warrants further investigation in human clinical trials. The upcoming trials using Daniell’s plant-based ACE2 delivery system will be critical in determining the applicability of these findings to human health.
FAQ
What are ACE inhibitors and ARBs? ACE inhibitors and ARBs are medications commonly prescribed to treat high blood pressure. ACE inhibitors prevent the body from producing angiotensin II, a substance that narrows blood vessels. ARBs block the action of angiotensin II, helping to relax blood vessels.
What is ACE2? ACE2 is an enzyme in the body that helps to lower blood pressure by converting angiotensin II into angiotensin 1-7, which promotes vasodilation. ACE2 is also a receptor used by the SARS-cov-2 virus to enter cells.
What did the study find? The study found that some ACE inhibitors can inhibit the activity of ACE2, while arbs can increase the level of angiotensin II.
Does this mean I should stop taking my blood pressure medication? No. Patients should never stop taking prescribed medication without first consulting their doctor. This study highlights the need for further research and personalized treatment approaches.
* What are the next steps for this research? The next steps include repeating the study with dogs on lisinopril and conducting human clinical trials to evaluate the benefits of ACE2 treatment.
