Monday, July 22, 2024

How does lisinopril work?

Lisinopril (Zestril) is a blood-pressure-lowering medication.1 How does lisinopril work, what is it used for, and what are the common side effects? 

Lisinopril is a prescription medication in the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is prescribed to help lower blood pressure in adults and children over the age of six who have high blood pressure, also known as hypertension.1

It is sometimes also used to treat congestive heart failure. 

Lisinopril may also be administered to stable patients within 24 hours of a heart attack, as it could potentially reduce the subsequent risk of mortality.2 

Lisinopril, along with other ACE inhibitors, is also generally more affordable than some other blood pressure-lowering medications; this could be helpful for people who do not have insurance.

How was lisinopril discovered?

Lisinopril is actually a long-lasting analog of another ACE inhibitor, called enalapril.3 

The fact that lisinopril only needs to be taken once a day whereas enalapril needs to be taken multiple times a day may help improve patient compliance; taking fewer pills generally helps reduce drug costs and improve convenience. 

Lisinopril was approved for use in the United States under the brand name Zestril in 1988.4

How does lisinopril work?

Angiotensin-converting enzyme (ACE) catalyzes the synthesis of angiotensin II, which constricts blood vessels .3 

Lisinopril and other ACE inhibitors work by inhibiting this enzyme, and in turn, facilitate a decrease in angiotensin II levels and an increased level of a hormone called bradykinin. 

The lowered angiotensin II levels are associated with a lower release of aldosterone, and this facilitates an increased rate of sodium and water excretion from the kidneys.5 

As a result, the dilation of blood vessels caused by increased bradykinin and a lack of angiotensin II increases the amount of space inside, and the decreased water retention caused by lower aldosterone levels decreases the overall blood volume and amount of fluid. 

Blood pressure is ultimately lowered by the increased space and decreased blood volume

The decreased blood pressure caused by lisinopril may also lower the risk of adverse cardiovascular events, such as heart attack and stroke, due to decreased strain on the cardiovascular system.1

This, in some cases, makes this medication helpful for the treatment of heart failure and the acute management of heart attacks.6

Side effects of lisinopril

A common side effect of lisinopril is a dry cough, and this is thought to be associated with increased levels of bradykinin.5

Other common side effects may include headache, angioedema, chest pain, and nausea or dizziness, among others.1

It may also cause hypotension or abnormally low blood pressure; for this reason, doctors generally prescribe a low starting dose of this medication and check in with their patients throughout the first couple of weeks of treatment.

Lisinopril may also increase the risk of hyperkalemia, which is an abnormally high presence of potassium in the blood, since decreased aldosterone levels may decrease the rate of potassium excretion.3 

For this reason, it is important to tell your doctor or pharmacist about any potassium supplements or potassium-based salt substitutes that you may be using.

Some studies suggest that the use of lisinopril and other ACE inhibitors could potentially increase the risk of hypoglycemia, or low blood sugar levels, in people with diabetes.7

This article is not medical advice, and it is not intended to prescribe, diagnose, or promote specific treatments for any condition.


  1. Rx Professional (2020 July 14). RxList. Retrieved 2021 March 1, from
  2. John. M. Eisenberg Center for Clinical Decisions and Communications Science (2010). “ACE Inhibitors” and “ARBs” to protect your heart?: A guide for patients being treated for stable coronary heart disease. Comparative Effectiveness Review Summary Guides for Consumers [Internet]. Retrieved 2021 March 1, from
  3. Lopez, E., et al (2020 December 2). Lisinopril. StatPearls [Internet]. Retrieved 2021 March 1, from
  4. Access Data: Drugs at FDA [pdf]. (2014). Food and Drug Administration. Retrieved 2021 March 1, from
  5. Klabunde, R.E., PhD. (2017 November 17). Cardiovascular Pharmacology Concepts. Retrieved 2021 March 1, from
  6. Goa, K.L., Balfour, J.A., Zuanetti, G. (1996). Lisinopril: a review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. Drugs 52(4): 564-588. Doi: 10.2165/00003495-199652040-00011
  7. Vue, M.H., PharmD, Setter, S.M., PharmD, CDE, CGP (2011). Drug-induced glucose alterations part 1: Drug-Induced Hypoglycemia (Pharmacy and Therapeutics). Diabetes Spectrum 24(3): 171-177.
  8. Image by Arek Socha from Pixabay 


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