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How do ACE Inhibitors work?

What are ACE inhibitors?

Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs that are used in the treatment and management of high blood pressure, heart failure, diabetic nephropathy and several other conditions.

ACE inhibitors can be used in combination with other drugs such as diuretics, depending on the severity of the condition.

All of the angiotensin-converting enzyme inhibitors are effective in the treatment of hypertension at equivalent doses.

Mechanism of action of ACE inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are vasodilators, they lower blood pressure by interfering with the renin-angiotensin-aldosterone system or by increasing levels of bradykinin.

In order to understand the mechanism of action of ACE inhibitors, you need to review the renin angiotensin aldosterone system (RAAS):

RAAS plays a central role in blood pressure regulation.

Renin is an enzyme that’s secreted by the kidneys in response to change in the GFR, amount of sodium in tubular fluid or arterial pressure, and it is responsible for conversion of angiotensinogen (which is produced by the liver) to angiotensin I.

Angiotensin I is then rapidly converted to angiotensin II by the angiotensin-converting enzyme (ACE). This enzyme is present in the blood vessels of the lungs.

Angiotensin II acts on the renal tubules and increases sodium reabsorption, it is a vasoconstrictor (and therefore it increases blood pressure).

Angiotensin II also regulates aldosterone levels, a hormone secreted by the adrenal cortex, which stimulate sodium reabsorption, thereby, increasing blood pressure.

angiotensinogen

How do ACE inhibitors work?

Angiotensin-converting enzyme inhibitors (ACEIs) act by decreasing systemic vascular resistance by preventing the conversion of angiotensin I to angiotensin II. This will lead to decreasing vasoconstriction and peripheral arterial resistance. It will also decrease secretion of aldosterone, which will reduce sodium and water retention and extracellular fluid volume.

ACE inhibitors and bradykinin

Bradykinin is a vasodilator which is present in body fluids. ACE is responsible for degradation of bradykinin, so inhibition of angiotensin-converting enzyme will increase bradykinin levels, which will lead to dilation of blood vessels, and thus decreasing blood pressure.

References

1.Carol Mattson Porth, Glenn Matifn/ Pathophysiology: Concepts of Altered Health States/ 8th edition/ Philadelphia, United States/ Lippincott Williams and Wilkins/ 2009

2.Anthony Trevor, Bertram Katzung, Marieke Knuidering-Hall/ Katzung & Trevor’s Pharmacology Examination & Board Review/ 11th edition/ United States/ McGraw-Hill Education-Europe/ 2015

3.Whalen, K., Finkel, R. and Panavelil, T.A. (2015). Pharmacology. Philadelphia: Wolters Kluwer.

4.Williams and Wolters Kluwer Health (2012). Nursing 2012 drug handbook. Philadelphia, Pa.: Wolters Kluwer Health/Lippincott Williams & Wilkins.

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