Review Question - QID 100762

Angiotensin converting enzyme (ACE) inhibitors, such as lisinopril, inhibit both the conversion of angiotensin I to angiotensin II as well as the degradation of bradykinin. Therefore, increased levels of bradykinin and decreased angiotensin II levels would be expected in a patient switching from losartan to lisinopril.

In the renin-angiotensin-aldosterone system, renin is released from the kidneys and converts angiotensinogen to angiotensin I. ACE converts angiotensin I to angiotensin II and also metabolizes bradykinin. Angiotensin II stimulates angiotensin-1 receptors (AT-1), which constrict vascular smooth muscle and increase aldosterone secretion in the adrenal cortex. In contrast to ACE inhibitors (discussed above), angiotensin receptor blockers (ARBs), such as losartan, mediate AT-1 receptor blockade that interferes with negative feedback and produces concomitant increases in renin, angiotensin I, and angiotensin II. AT-1 receptor blockade should not affect bradykinin levels.

Bui discusses the findings of a large meta-analysis of first-line medications for hypertension. While thiazide diuretics, ACE-inhibitors, and calcium channel blockers are demonstrated reduced stroke and cardiovascular events, only thiazide diuretics and ACE-inhibitors demonstrated reduced mortality.

Li et al. compare the use of ACE inhibitors versus ARBs for the treatment of primary hypertension. There is no difference in mortality or cardiovascular outcomes between patients treated with these two different classes of drugs. ACE inhibitors have been shown to be effective in comparison to placebo; however, no such studies have been conducted for ARBs in assessing placebo-controlled trials for hypertension.

Illustration A summarizes the renin-angiotensin-aldosterone system. Illustration B depicts the mechanism of action of ACE inhibitors. Illustration C displays a mnemonic useful for memorizing the potential side effects of ACE inhibitors.

Incorrect Answers:
Answer 2: Angiotensin I would be expected to increased with an ACE inhibitor; however, renin would be expected to increase as well given feedback mechanisms and the blockade of a 'downstream' enzyme.
Answer 3: Aldosterone is 'downstream' from the inhibition of ACE and would be decreased; concomitantly, bradykinin would be expected to increase given its decreased breakdown in the setting of ACE inhibitor therapy.
Answer 4: ACE inhibitors block conversion of angiotensin I to angiotensin II, resulting in decreased angiotensin II levels.
Answer 5: ACE inhibitors block conversion of angiotensin I to angiotensin II, resulting in decreased angiotensin II levels; ACE inhibitors lead to decreased breakdown of bradykinin, resulting in build-up of bradykinin.