Angiotensin II is a very potent chemical produced by the body that primarily circulates in the blood. It causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing increases in blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme (ACE). (Angiotensin I in the blood is itself formed from angiotensinogen, a protein produced by the liver and released into the blood.)
Angiotensin converting enzyme inhibitors (ACE inhibitors) are medications that slow (inhibit) the activity of the enzyme ACE, which decreases the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed.
An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure.
This group of drugs causes relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. They inhibit the angiotensin-converting enzyme, an important component of the renin–angiotensin system.
Frequently prescribed ACE inhibitors include benazepril, zofenopril, perindopril, trandolapril, captopril, enalapril, lisinopril, and ramipril.
Angiotensin-converting enzyme (ACE) inhibitors help relax blood vessels. ACE inhibitors prevent an enzyme in your body from producing angiotensin II, a substance in your body that narrows your blood vessels and releases hormones that can raise your blood pressure. This narrowing can cause high blood pressure and force your heart to work harder.
They also raise blood flow, which helps to lower your heart’s workload.
Examples of ACE inhibitors include:
- Accupril (quinapril)
- Aceon (perindopril)
- Altace (ramipril)
- Capoten (captopril)
- Lotensin (benazepril)
- Mavik (trandolapril)
- Monopril (fosinopril)
- Prinivil, Zestril (lisinopril)
- Univasc (moexipril)
- Vasotec (enalapril)
- Benazepril (Lotensin)
- Enalapril (Vasotec)
- Lisinopril (Prinivil, Zestril)
- Perindopril (Aceon)
- Quinapril (Accupril)
- Ramipril (Altace)
- Trandolapril (Mavik)
Angiotensin formation and actionsACE inhibitors produce vasodilation by inhibiting the formation of angiotensin II. This vasoconstrictor is formed by the proteolytic action of renin (released by the kidneys) acting on circulating angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme.
ACE also breaks down bradykinin (a vasodilator substance). Therefore, ACE inhibitors, by blocking the breakdown of bradykinin, increase bradykinin levels, which can contribute to the vasodilator action of ACE inhibitors. The increase in bradykinin is also believed to be responsible for a troublesome side effect of ACE inhibitors, namely, a dry cough.
Angiotensin II constricts arteries and veins by binding to AT1 receptors located on the smooth muscle, which are coupled to a Gq-protein and the the IP3 signal transduction pathway. Angiotensin II also facilitates the release of norepinephrine from sympathetic adrenergic nerves and inhibits norepinephrine reuptake by these nerves. This effect of angiotensin II augments sympathetic activity on the heart and blood vessels.
Will My ACE Inhibitor Interact With Any Foods or Drugs?
It can. Don’t use salt substitutes if you’re taking one. They contain potassium, and ACE inhibitor medications cause the body to retain that. Read your labels to choose foods low in salt and potassium. A dietitian can help, too.
Over-the-counter nonsteroidal anti-inflammatory medications (NSAIDs, like Aleve and Motrin) and aspirin may cause your body to retain salt and water, and decrease the effect of an ACE inhibitor. Check with your doctor before taking any anti-inflammatories.
It’s important for your doctor to know about all the drugs you are taking. Some, in addition to those above, may not work well with ACE inhibitors.
Talk to your doctor before taking any new medicines, including over-the-counter drugs, herbs, and supplements.
What Are the Side Effects?
Possible ones include:
Cough: If this persists or is severe, contact your doctor. Ask what type of cough medicine you can use to ease it.
Red, itchy skin rash: If you have this, don’t treat the rash yourself. Call your doctor.
Dizziness, lightheadedness, or faintness when you get up: This may be strongest after your first dose, especially if you’ve been taking a water pill (diuretic). Get up more slowly. If it keeps up, reach out to your medical team.
Salty or metallic taste, or a decreased ability to taste: This usually goes away as you continue taking the medicine.
Physical symptoms: Call your doctor if you have:
- Sore throat
- Mouth sores
- Unusual bruising
- Fast or irregular heartbeat
- Chest pain
- Swelling of feet, ankles, or lower legs
Swelling of your neck, face, and tongue: Contact your doctor right away if you have any of these. This is a potential emergency.
High potassium levels: This is a potentially life-threatening complication. Therefore, people on ACE inhibitors should have blood tests regularly to measure potassium levels.
Signs of too much in your body include:
- Irregular heartbeat
- Numbness or tingling in hands, feet, or lips
- Shortness of breath or difficulty breathing
- Weakness or heaviness in your legs
Contact your doctor right away if you have any of these.
Severe vomiting or diarrhea: These can make you dehydrated. That can lead to low blood pressure. Call your doctor right away.
Also reach out to your medical team if you have any other symptoms that concern you.
Cardiorenal Effects of ACE Inhibitors
Vasodilation (arterial & venous)
- reduce arterial & venous pressure
- reduce ventricular afterload & preload
Decrease blood volume
Depress sympathetic activity
Inhibit cardiac and vascular hypertrophy
ACE inhibitors have the following actions:
Dilate arteries and veins by blocking angiotensin II formation and inhibiting bradykinin metabolism. This vasodilation reduces arterial pressure, preload and afterload on the heart.
Down regulate sympathetic adrenergic activity by blocking the facilitating effects of angiotensin II on sympathetic nerve release and reuptake of norepinephrine.
Promote renal excretion of sodium and water (natriuretic and diuretic effects) by blocking the effects of angiotensin II in the kidney and by blocking angiotensin II stimulation of aldosterone secretion. This reduces blood volume, venous pressure and arterial pressure.
Inhibit cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction.
Elevated plasma renin is not required for the actions of ACE inhibitors, although ACE inhibitors are more efficacious when circulating levels of renin are elevated. We know that renin-angiotensin system is found in many tissues, including heart, brain, vascular and renal tissues. Therefore, ACE inhibitors may act at these sites in addition to blocking the conversion of angiotensin in the circulating plasma.
Can Pregnant Women Take Them?
Women should not take them during pregnancy, especially during the second and third trimesters. They can lower blood pressure and cause kidney failure or high potassium levels in the blood of the mother. They can cause death or deformity in the newborn.
Babies shouldn’t be breastfed if the mother is taking an ACE inhibitor. The medicine can pass through breast milk.
Can Children Take Them?
The short answer is yes. However, kids are more sensitive to the effects of them on their blood pressure. So, they’re at higher risk of severe side effects.
Before giving an ACE inhibitor to a child, discuss the potential benefits and risks with your pediatric cardiologist (heart doctor).
For what conditions are ACE inhibitors used?
ACE inhibitors are effective for control of blood pressure, congestive heart failure, and prevention of stroke and hypertension, or diabetes-related kidney damage. ACE inhibitors are especially important because they have been shown to prevent early death resulting from hypertension, heart failure or heart attacks; in studies of patients with hypertension, heart failure, or prior heart attacks, patients who received an ACE inhibitor survived longer than patients who did not receive an ACE inhibitor. ACE inhibitors may be combined with other drugs to achieve optimal blood pressure control.
ACE inhibitors are used for:
- Controlling acute and chronic high blood pressure
- Treating left ventricular dysfunction and heart failure
Preventing and treating kidney disease (nephropathy) in people with hypertension or diabetes
- ACE inhibitors also improve survival after heart attacks. In studies, individuals with hypertension, heart failure, or prior heart attacks who were treated with an ACE inhibitor lived longer than patients who did not take an ACE inhibitor.
- ACE inhibitors are an important group of drugs because they prevent early death resulting from hypertension, heart failure or heart attacks.
- Some individuals with hypertension do not respond sufficiently to ACE inhibitors alone. In these cases, other drugs often are used in combination with ACE inhibitors.
How do ACE inhibitors work?
ACE inhibitors block your body from producing a chemical called angiotensin II. When angiotensin II enters your blood stream your blood vessels become narrower. This gives your blood less space to move in, which raises your blood pressure.
Angiotensin II also triggers a hormone that makes your body retain water. Having more fluid in your body, in a restricted space, will cause your blood pressure to rise. ACE inhibitors lower your blood pressure by reducing angiotensin II in your body. This allows your blood vessels to relax and widen, making it easier for blood to flow through. It also lowers the amount of water your body retains, which lowers your blood pressure.
ACE inhibitors action is to reduce the amount of angiotensin II produced. Usually angiotensin II has an effect on the body to increase blood pressure, increase blood volume and increase pressure in the kidney. As the ACE inhibitor lowers the amount of angiotensin II, this causes the blood vessels to become wider and there is an increase in the amount of urine produced by the kidneys. The result of this is the blood pressure goes down, blood volume decreases and there is a reduction of pressure in the kidney. The lowering of angiotensin II levels by ACE inhibitors also causes a drop in noradrenalin and aldosterone levels, which helps to reduce blood pressure. Another effect ACE inhibitors have is to increase bradykinin which also causes the blood vessels to widen with a further decrease in blood pressure.
The most common side effects are:
- Elevated blood potassium levels
- Low blood pressure,
- Loss of appetite
- Skin rashes or blisters
- Joint pain
- Abnormal taste (metallic or salty taste)
- Chest pain
- Increased uric acid levels
- Sun sensitivity
- Increased BUN and creatinine levels
- It may take up to a month for coughing to subside, and if one ACE inhibitor causes cough it is likely that the others will too.
- The most serious, but rare, side effects of ACE inhibitors are:
- Kidney failure
- Allergic reactions
- Liver dysfunction
- A decrease in white blood cells
- Swelling of tissues (angioedema).
The first ACE inhibitor marketed, captopril, is still in widespread use today. Although newer ACE inhibitors differ from captopril in terms of pharmacokinetics and metabolism, all the ACE inhibitors have similar overall effects on blocking the formation of angiotensin II. ACE inhibitors include the following specific drugs:
Therapeutic Use of ACE Inhibitors
- Heart failure
- Post-myocardial infarction
ACE inhibitors are considered “first-line therapy” in the treatment of stage 1 hypertension. They may also be used in hypertension caused by renal artery stenosis, which causes renin-dependent hypertension owing to the increased release of renin by the kidneys. Reducing angiotensin II formation leads to arterial and venous dilation, which reduces arterial and venous pressures. By reducing the effects of angiotensin II on the kidney, ACE inhibitors cause natriuresis and diuresis, which decreases blood volume and cardiac output, thereby lowering arterial pressure.
African Americans do not respond as well as other races to monotherapy with ACE inhibitors or angiotensin receptor blockers (ARBs); however, differences in blood pressure lowering efficacy are eliminated with adequate diuretic dosing. Therefore, current recommendations are that ACE inhibitors and ARBs are appropriate for use in African Americans, but not as monotherapy. A diuretic or calcium-channel blocker should be used with an ACE inhibitor or ARB to achieve the target reduction in blood pressure.
ACE inhibitors have proven to be very effective in the treatment of heart failure caused by systolic dysfunction (e.g., dilated cardiomyopathy). Beneficial effects of ACE inhibition in heart failure include:
- Reduced afterload, which enhances ventricular stroke volume and improves ejection fraction.
- Reduced preload, which decreases pulmonary and systemic congestion and edema.
- Reduced sympathetic activation, which has been shown to be deleterious in heart failure.
- Improving the oxygen supply/demand ratio primarily by decreasing demand through the reductions in afterload and preload.
- Prevents angiotensin II from triggering deleterious cardiac remodeling.
Finally, ACE inhibitors have been shown to be effective in patients following myocardial infarction because they help to reduce deleterious remodeling that occurs post-infarction.
ACE inhibitors are often used in conjunction with a diuretic in treating hypertension and heart failure.
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