How do Angiotensin-Converting Enzyme (ACE) inhibitors decrease preload and afterload on the heart?

From the Guidelines

ACE inhibitors decrease both preload and afterload on the heart through several mechanisms, including blocking the conversion of angiotensin I to angiotensin II, causing vasodilation of arteries and veins, and decreasing aldosterone production, which leads to decreased sodium and water retention by the kidneys. These medications, such as lisinopril, enalapril, ramipril, and captopril, are valuable in treating conditions like heart failure, hypertension, and post-myocardial infarction, as they reduce the workload on the heart and improve cardiac output 1. The most recent and highest quality study, published in 2017, recommends the use of ACE inhibitors to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) 1.

Mechanisms of Action

• Block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor
• Cause vasodilation of both arteries and veins, reducing peripheral vascular resistance and increasing venous capacitance
• Decrease aldosterone production, leading to decreased sodium and water retention by the kidneys
• Reduce the amount of blood returning to the heart, thereby decreasing preload, and reduce the pressure against which the heart must pump, thereby decreasing afterload

Clinical Use

• Typical starting doses are lower (such as lisinopril 2.5-5mg daily) with gradual titration upward as tolerated, while monitoring blood pressure and kidney function
• Should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials
• Can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium (>5.0 mEq/L) 1

Recommendations

• The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality 1
• ACE inhibitors should be used in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients 1
• ARBs can be used as an alternative to ACE inhibitors in patients who are intolerant to ACE inhibitors due to cough or angioedema 1

From the FDA Drug Label

ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.

Decrease in Preload and Afterload:

• Preload: The decrease in preload is likely due to the decreased vasopressor activity of angiotensin II, which leads to vasodilation of blood vessels, reducing the amount of blood returning to the heart.
• Afterload: The decrease in afterload is also due to the decreased vasopressor activity of angiotensin II, which leads to vasodilation of blood vessels, reducing the resistance the heart must pump against to eject blood into the circulation 2.

From the Research

Mechanism of Action of ACE Inhibitors

• ACE inhibitors reduce preload and afterload on the heart by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor 3, 4
• Angiotensin II also promotes sodium and water retention, which increases blood volume and pressure 4
• By reducing the levels of angiotensin II, ACE inhibitors promote vasodilatation and reduce intravascular fluid volume, leading to a decrease in blood pressure 4, 5

Effects on Preload and Afterload

• Preload is reduced by decreasing the amount of blood returning to the heart, which is achieved by reducing venous tone and increasing venous capacitance 3
• Afterload is reduced by decreasing the resistance to blood flow in the arteries, which is achieved by relaxing the smooth muscle in the arterial walls 3, 4
• The reduction in preload and afterload leads to a decrease in the workload of the heart, which can improve cardiac output and reduce the risk of heart failure 3, 6

Clinical Benefits

• ACE inhibitors have been shown to be effective in reducing the risk of cardiovascular morbidity and mortality, particularly in high-risk individuals 3
• They are also useful in the treatment of congestive heart failure, acute myocardial infarction, and coronary artery disease 3, 7
• The use of ACE inhibitors can also slow the progression of kidney disease, especially in patients with diabetes 3