Lisinopril is not a nitrate. It belongs to a completely different class of medications called ACE inhibitors (angiotensin-converting enzyme inhibitors). While both lisinopril and nitrates are used to treat cardiovascular conditions, they work through entirely different mechanisms in the body and are not interchangeable.
What Lisinopril Actually Is
Lisinopril is classified by the FDA as an oral, long-acting ACE inhibitor. It works by blocking an enzyme that converts a hormone called angiotensin I into angiotensin II. Angiotensin II is a powerful substance that narrows blood vessels and triggers the release of another hormone, aldosterone, which causes the body to hold onto sodium and water. By blocking this chain reaction, lisinopril relaxes blood vessels and reduces fluid retention, lowering blood pressure.
Lisinopril is approved for three main uses: treating high blood pressure, managing heart failure alongside other medications, and improving survival after a heart attack. It’s taken as a once-daily pill, with typical doses ranging from 10 to 40 mg for high blood pressure and 5 to 40 mg for heart failure.
What Nitrates Are
Nitrates are a separate family of medications that include nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. These drugs work by activating a signaling pathway inside cells that causes blood vessels to relax and widen. Nitrates primarily dilate veins, which reduces the amount of blood returning to the heart and lowers the heart’s workload. They also widen the coronary arteries that supply blood to the heart muscle itself.
Nitrates come in many forms: sublingual tablets you dissolve under your tongue, sprays, patches, ointments, capsules, and intravenous solutions. They’re most commonly used for chest pain (angina) and acute heart failure. Nitroglycerin tablets placed under the tongue during a chest pain episode are probably the most recognized use of this drug class.
How Their Mechanisms Differ
The confusion between these two drugs likely comes from the fact that both lower blood pressure and both affect blood vessels. But they do so through completely unrelated pathways.
Lisinopril targets the renin-angiotensin-aldosterone system, a hormonal cascade that regulates blood pressure and fluid balance over hours and days. It blocks the production of a vasoconstricting hormone, so its effects build gradually and persist with daily use. ACE inhibitors also reduce sodium retention in the kidneys and can raise potassium levels.
Nitrates, by contrast, work by releasing nitrogen oxide compounds that directly signal smooth muscle cells in blood vessel walls to relax. This effect is more immediate, which is why nitroglycerin can relieve chest pain within minutes. However, nitrates are prone to tolerance, meaning the body can stop responding to them in as little as four hours of continuous intravenous use.
Side Effects Set Them Apart
The side effect profiles of these two drug classes are distinctly different, which is another way to tell them apart. ACE inhibitors like lisinopril are well known for causing a persistent dry cough, a side effect that doesn’t occur with nitrates. Lisinopril can also raise potassium levels and, in rare cases, cause a serious swelling reaction called angioedema.
Nitrates, on the other hand, commonly cause headaches due to the dilation of blood vessels in the head. Interestingly, research on older adults found that people taking ACE inhibitors alongside nitrates were about half as likely to develop nitrate-induced headaches compared to those not on ACE inhibitors. In a study of over 1,500 hospitalized patients, headaches occurred in 1.6% of those on ACE inhibitors versus 3.2% of those who were not.
Can You Take Both Together?
Lisinopril and nitrates are sometimes prescribed together, particularly for people with heart failure or those recovering from a heart attack. Because both medications lower blood pressure through different pathways, combining them can cause blood pressure to drop more than either drug alone. This additive effect is generally manageable when doses are adjusted appropriately, but it means you should be aware of symptoms like dizziness or lightheadedness when standing up.
The important drug interaction to know about with nitrates involves a different class entirely: PDE5 inhibitors used for erectile dysfunction. Combining nitrates with those medications can cause a dangerous drop in blood pressure. Lisinopril does not carry this same restriction.
Quick Reference: Lisinopril vs. Nitrates
- Drug class: Lisinopril is an ACE inhibitor; nitroglycerin and isosorbide are nitrates
- How they work: Lisinopril blocks a hormone that constricts blood vessels; nitrates release compounds that directly relax vessel walls
- Speed of action: Lisinopril works gradually over hours to days; sublingual nitrates can work within minutes
- How they’re taken: Lisinopril is a once-daily pill; nitrates come as pills, patches, sprays, ointments, or IV solutions
- Common side effects: Lisinopril causes dry cough and elevated potassium; nitrates cause headaches and tolerance with prolonged use
- Primary uses: Lisinopril treats high blood pressure, heart failure, and post-heart attack recovery; nitrates treat chest pain and acute heart failure