What is the mechanism by which lisinopril (angiotensin-converting enzyme inhibitor) lowers blood pressure in patients with hypertension?

From the Guidelines

Lisinopril lowers blood pressure by blocking the action of angiotensin-converting enzyme (ACE), which prevents the formation of angiotensin II, a powerful blood vessel constrictor, as supported by the most recent and highest quality study 1. This causes blood vessels to relax and widen, reducing resistance to blood flow and lowering blood pressure.

• The mechanism of action of lisinopril is well-established, and its effectiveness in reducing blood pressure has been consistently demonstrated in various studies, including the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1.
• Lisinopril is typically started at 10 mg once daily for hypertension, though some patients may begin at 5 mg, especially those who are elderly or taking diuretics.
• The dose can be adjusted every 1-2 weeks based on blood pressure response, with a usual maintenance dose of 20-40 mg daily and a maximum of 80 mg daily.
• Lisinopril should be taken at the same time each day to maintain consistent blood levels.
• It may take several weeks to see the full blood pressure-lowering effect.
• Common side effects include dry cough, dizziness, and headache.
• Patients should be aware that lisinopril can cause a significant drop in blood pressure when starting treatment, especially after the first dose, so it's advisable to take the first dose at bedtime.
• Additionally, potassium levels should be monitored as lisinopril can increase potassium in the blood, as noted in the 2007 guidelines for the management of arterial hypertension 1.
• The use of ACE inhibitors, such as lisinopril, is beneficial for patients with prior or current symptoms of chronic heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, as recommended by the 2017 ACC/AHA/HFSA focused update 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion.

Lisinopril lowers blood pressure by:

• Inhibiting angiotensin-converting enzyme (ACE)
• Decreasing plasma angiotensin II
• Decreasing vasopressor activity
• Decreasing aldosterone secretion This results in a reduction of both supine and standing blood pressure with no compensatory tachycardia 2.

From the Research

Mechanism of Action

• Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that lowers blood pressure by reducing peripheral vascular resistance 3, 4, 5, 6.
• It works by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing plasma angiotensin II and aldosterone levels 6.
• This leads to a decrease in blood pressure without affecting heart rate or cardiovascular reflexes 6.

Pharmacokinetics

• Lisinopril is absorbed orally, with a bioavailability of approximately 25% 6.
• It is not metabolized and is excreted unchanged in the urine, with a half-life of 12.6 hours in normotensive individuals 3.
• The onset of action occurs within 1-2 hours, and the effects last for at least 24 hours, allowing for once-daily dosing 3, 6.

Efficacy

• Lisinopril has been shown to be effective in lowering blood pressure in patients with essential hypertension, with a comparable efficacy to other antihypertensive agents such as hydrochlorothiazide, atenolol, metoprolol, and nifedipine 3, 4, 5, 6.
• It has also been shown to be effective in patients with congestive heart failure, with improved indices of cardiac function and a potential greater benefit than captopril in one controlled study 4.
• The addition of hydrochlorothiazide to lisinopril can enhance its antihypertensive effect, and lisinopril can also attenuate hypokalemia induced by thiazide diuretics 4, 6.