Can Lisinopril Cause a Low Heart Rate?

Lisinopril, on its own, is not expected to cause a low heart rate. The drug belongs to the ACE inhibitor class, and its primary pharmacological action is to lower blood pressure by relaxing blood vessels, not by slowing the heart. Clinical pharmacology data show that lisinopril produces a gradual reduction in blood pressure “without affecting heart rate or cardiovascular reflexes.”¹ That said, there are real scenarios where people taking lisinopril do end up with a slower-than-normal pulse, and they tend to involve other medications, kidney problems, or shifts in the nervous system that deserve a closer look.

How Lisinopril Lowers Blood Pressure Without Targeting Heart Rate

Lisinopril works by blocking angiotensin-converting enzyme, the enzyme responsible for producing a powerful blood-vessel-constricting hormone. With less of that hormone circulating, your blood vessels relax and widen, reducing the resistance your heart has to pump against. This is a fundamentally different approach from drugs like beta-blockers, which directly slow the heart. ACE inhibitors decrease the resistance in your blood vessels without increasing heart rate, and they promote the excretion of sodium and water.² Because lisinopril does not directly act on the electrical system or muscle of the heart, nursing guidelines note that routine heart rate measurement before giving the drug is not typically performed, unlike with beta-blockers.³

This is an important distinction. When your blood pressure drops because a drug has widened your arteries, your body’s normal reflex is to speed the heart up slightly to compensate. Many blood-pressure-lowering drugs trigger exactly that reflex. With lisinopril, the blood pressure drop is gentle enough that the compensatory heart rate increase essentially doesn’t happen, and the heart rate stays roughly where it was before treatment. That is actually considered one of the advantages of ACE inhibitors: they lower blood pressure smoothly without the unwanted racing pulse that some other medications can produce.

The Vagal Tone Effect

Even though lisinopril doesn’t directly slow the heart, ACE inhibitors as a class can influence the branch of the nervous system that does. Your vagus nerve acts as a natural brake on heart rate, and the strength of that braking signal is called vagal tone. In people with heart failure, ACE inhibitors have been shown to increase vagal tone significantly, essentially strengthening the body’s own heart-slowing signal.⁴ Researchers have viewed this as a good thing: higher vagal tone is associated with a better prognosis in heart failure and may protect against dangerous heart rhythms.

The practical question is whether this increased vagal tone is strong enough to actually slow someone’s heart rate to a noticeable degree. For most people taking lisinopril, the answer is no. Studies comparing lisinopril and a related drug, valsartan, in people with chronic heart failure found that lisinopril influenced vagal control of heart rate in a measurable way, but the effect on actual resting heart rate was not clinically dramatic.⁵ However, if you’re someone whose vagal tone is already on the higher side, or if other factors are at play, this shift could potentially nudge your resting pulse lower than usual. It’s a subtle mechanism and not one that shows up in most people’s day-to-day experience with the drug.

When Other Medications Are the Real Culprit

The scenario where lisinopril is most closely linked to a dangerously low heart rate almost always involves another drug in the picture. The combination of an ACE inhibitor with a beta-blocker is extremely common in cardiology, used in conditions ranging from high blood pressure to heart failure to post-heart-attack care. Beta-blockers and ACE inhibitors work on different parts of the cardiovascular system: the beta-blocker directly slows the heart and reduces how forcefully it contracts, while the ACE inhibitor opens up blood vessels and reduces fluid retention.⁶ Together they provide comprehensive blockade of the stress-hormone systems that drive heart disease.

The trade-off is that combining these two types of drugs means layering a direct heart-slowing agent on top of something that can subtly enhance the body’s own heart-slowing signals. In most patients, this is well-tolerated and intentional. But when kidney function declines, potassium rises, or another medication enters the mix, things can tip into trouble. Published case reports describe a 77-year-old woman on both lisinopril and metoprolol (a common beta-blocker) who developed a heart rate of 38 beats per minute alongside kidney failure and dangerously high potassium. This cluster of problems has been given an acronym, BRASH syndrome, which stands for bradycardia, renal failure, AV-nodal blockers, shock, and hyperkalemia. It represents a vicious cycle: the beta-blocker slows the heart, kidney impairment prevents potassium from being excreted, the rising potassium further suppresses heart rate, and the ACE inhibitor contributes by raising potassium levels and potentially accumulating in the body as kidneys falter.

Another striking case involved an 85-year-old man who had been taking lisinopril for years without heart rate problems. When he was prescribed tizanidine, a muscle relaxant that also lowers blood pressure through a completely different mechanism, his heart rate plummeted to 37 beats per minute and his blood pressure crashed. Tizanidine has its own blood-pressure-lowering and sedative effects, and combining it with an ACE inhibitor in a vulnerable older adult triggered a severe reaction that neither drug would have caused alone. In both of these cases, the low heart rate wasn’t really caused by lisinopril in isolation; it was the interaction between lisinopril and another medication, often amplified by kidney problems or electrolyte disturbances.

The Kidney Connection

Your kidneys play a bigger role in this story than you might expect. Lisinopril is eliminated from the body entirely through the kidneys. It isn’t broken down by the liver. This means that if your kidneys aren’t working well, lisinopril can build up to higher-than-intended levels in your blood. Research in patients with severe kidney impairment confirmed that lisinopril accumulates when renal function is poor, and that potassium levels tend to rise in these patients as well.⁷

The potassium piece matters because potassium directly affects how your heart’s electrical system works. When potassium climbs too high, the heart’s pacemaker cells slow down, and the signals that coordinate each heartbeat can become sluggish or irregular. ACE inhibitors, including lisinopril, reduce the amount of aldosterone your body makes. Aldosterone is the hormone that tells your kidneys to hang on to sodium and get rid of potassium. With less aldosterone, you retain more potassium. In someone with healthy kidneys, this slight rise in potassium is easily managed. In someone whose kidneys are already struggling, the combination of drug accumulation and rising potassium can create the conditions for a genuinely slow heart rate, especially if a beta-blocker or another heart-rate-lowering drug is also on board.

This is why doctors monitor kidney function and potassium levels when prescribing ACE inhibitors, particularly in older adults, people with diabetes, and anyone with known kidney disease. A slow heart rate in someone on lisinopril should prompt a check of these lab values before anything else.

What About Overdose

ACE inhibitor overdoses are uncommon but do occur, and the heart rate response is worth knowing about. When people take too much of an ACE inhibitor, the main problem is a steep drop in blood pressure. You might expect the heart to respond by racing faster to compensate. In practice, studies of ACE inhibitor overdoses found that heart rate did not increase substantially in response to the blood pressure drop.⁸ This means someone who has overdosed may have very low blood pressure and a heart rate that is paradoxically normal or even slow, rather than fast. That’s an important pattern for emergency providers to recognize, because the absence of a rapid pulse doesn’t mean the overdose isn’t serious.

This blunted heart rate response in overdose fits with what we know about how ACE inhibitors work: they dial down some of the reflex mechanisms that would normally speed the heart up when blood pressure falls. It’s not that they actively slam the brakes on heart rate, but they dampen the body’s normal accelerator response, which can leave the pulse inappropriately low for the situation.

Exercise Heart Rate on Lisinopril

A common concern for people who exercise is whether lisinopril will affect how high their heart rate can climb during a workout. Data from patients with heart failure and chronic atrial fibrillation showed that heart rate during exercise and during ambulatory monitoring was not significantly affected by lisinopril treatment.⁹ This stands in clear contrast to beta-blockers, which can meaningfully cap how high your heart rate reaches during exertion and sometimes leave people feeling sluggish during exercise.

If you’re taking lisinopril alone and notice that your heart rate seems unusually low during workouts, that’s less likely to be the lisinopril and more likely to be something else: improved cardiovascular fitness over time, dehydration, an unrelated thyroid issue, or another medication. Athletes and regular exercisers naturally develop lower resting heart rates as their heart becomes more efficient, and it’s easy to attribute that change to a medication you recently started.

A Randomized Trial That Showed Some Heart Rate Reduction

The picture isn’t entirely one-sided. One randomized, double-blind trial comparing lisinopril to nebivolol (a beta-blocker) in people with high blood pressure found that both treatments produced a statistically significant reduction in heart rate over the course of the study, with no difference between the two drugs in that regard.¹⁰ That finding is a bit surprising given that the bulk of ACE inhibitor research characterizes these drugs as heart-rate-neutral. It’s worth noting that the heart rate reduction in this trial appeared alongside significant blood pressure drops in both groups, and in clinical practice any meaningful blood pressure reduction can be accompanied by small shifts in heart rate simply because the cardiovascular system is settling into a new equilibrium. The magnitude of heart rate change in the lisinopril group was not described as clinically concerning, but the finding is a useful reminder that “no effect on heart rate” in pharmacology textbooks reflects a general trend, not an absolute rule for every individual.

This is one of those spots where the evidence is more nuanced than either a drug label or a brief Google result would suggest. Most studies say lisinopril leaves heart rate alone. At least one well-designed trial found a modest heart rate reduction. For the average person, the practical difference is negligible, but it may help explain why some individuals feel like their pulse has dipped a bit after starting the drug.

Heart Failure, Adrenergic Drive, and Receptor Changes

In people with heart failure, lisinopril does something interesting at the cellular level. A placebo-controlled study found that lisinopril therapy was associated with a significant increase in the density of beta-receptors on heart muscle cells, without significant changes in the heart’s adrenergic drive or in overall hemodynamics like heart rate or blood pressure.¹¹ Beta-receptors are the docking sites on heart cells where adrenaline and similar stress hormones land to make the heart beat faster and harder. In heart failure, these receptors get downregulated because the body is flooding the heart with stress hormones around the clock. By easing the workload on the heart and reducing the hormonal overdrive, lisinopril allows those receptors to recover.

What this means for heart rate is indirect. A heart with more beta-receptors available is theoretically more responsive to adrenaline when it’s genuinely needed, like during exercise or stress. But the overall effect of ACE inhibitor therapy in heart failure is to dial down the chronic stress-hormone barrage, which could leave the resting heart rate a touch lower simply because the heart isn’t being constantly goaded. Again, in clinical measurements this hasn’t translated into a dramatic heart rate change, but it represents one more pathway through which the drug subtly modifies the systems that control heart rate.

Genetic Variation in ACE Inhibitor Response

Not everyone responds to ACE inhibitors in the same way, and some of that variation is genetic. The gene for ACE itself comes in different forms. One well-studied variant is the insertion/deletion polymorphism: depending on which version you carry, your baseline ACE activity and your response to ACE inhibitors can differ. Research in heart failure patients found that this genetic variant significantly influenced how much blood pressure dropped with one ACE inhibitor (captopril) but did not significantly affect the blood pressure response to lisinopril.¹² The implication is that lisinopril’s effect may be more consistent across genetic backgrounds than some other ACE inhibitors, though this was a relatively small study and the field of pharmacogenomics in ACE inhibitor therapy is still evolving.

For the question of heart rate specifically, no strong genetic predictor has been identified that would tell you in advance whether lisinopril will slow your pulse. The genetic work has focused mostly on blood pressure response and kidney-related side effects. But the broader point stands: individual variation in drug response is real, and a medication that is heart-rate-neutral for the vast majority of people might produce a slightly different result in you because of your particular biology.

Practical Red Flags Worth Knowing

If you’re taking lisinopril and notice a resting heart rate consistently below 60 beats per minute, or if you’re experiencing dizziness, lightheadedness, unusual fatigue, or near-fainting episodes, a few questions are worth exploring with your healthcare provider:

Other medications: Are you also taking a beta-blocker, a calcium channel blocker like diltiazem or verapamil, digoxin, or a centrally acting drug like clonidine or tizanidine? Any of these can slow heart rate directly, and the combination with lisinopril can amplify the effect.
Kidney function: Have your kidneys been checked recently? Declining kidney function can cause lisinopril to accumulate and potassium to rise, both of which can contribute to a slower heart rate.
Potassium levels: High potassium is a common thread in cases where ACE inhibitors are involved in bradycardia. A simple blood test can rule this in or out quickly.
Thyroid function: An underactive thyroid can cause a slow heart rate on its own and is sometimes discovered when someone starts investigating a low pulse they attributed to medication.

The key pattern in published case reports is that lisinopril-associated bradycardia is rarely a one-factor problem. It almost always involves a second drug, a kidney issue, an electrolyte disturbance, or some combination of the three. Older adults are disproportionately affected because they’re more likely to be on multiple medications and more likely to have some degree of kidney impairment. If you’re younger, have healthy kidneys, and take lisinopril as your only heart or blood pressure medication, the chance of it meaningfully lowering your heart rate is quite small.