Review Question - QID 217046

This patient with a history of diabetes mellitus presents with hypertension and is started on an anti-hypertensive medication that causes a dry cough. This side effect is characteristic of an angiotensin-converting enzyme (ACE) inhibitor, which causes an increase in renin and angiotensin I levels and a decrease in angiotensin II and aldosterone levels.

In the renin-angiotensin-aldosterone system, hypotension or decreased sodium delivery to the kidneys causes renin release by juxtaglomerular cells. Renin converts angiotensinogen into angiotensin I, which is subsequently converted into angiotensin II by ACE. Angiotensin II causes vasoconstriction, renal sodium retention, and aldosterone release by the adrenal cortex. ACE inhibitors work by inhibiting ACE, thus resulting in a buildup of the upstream molecules renin and angiotensin I and reduced production of the downstream molecules angiotensin II and aldosterone. ACE inhibitors are preferred in hypertensive patients with comorbid diabetes due to their protective effects against diabetic nephropathy. ACE inhibitors can cause a dry cough by preventing the deactivation of bradykinin. Patients who develop a dry cough on ACE inhibitors can be switched to angiotensin II receptor blockers (ARBs), which do not have this side effect.

Sato and Fukuda studied the incidence of cough in hypertensive patients treated with ACE inhibitors. They found that cough was present in 20% of their study cohort, more often in women, and resulted in the discontinuation of the ACE inhibitor in 5% of patients.

Figure A is a table showing the answer choices with changes in renin, angiotensin I, angiotensin II, and aldosterone levels.

Incorrect Answers:
Answer 1: Increased renin, angiotensin I, angiotensin II, and aldosterone levels may be seen with use of an aldosterone antagonist such as spironolactone. Spironolactone can be used in resistant hypertension and may cause hyperkalemia, which can result in palpitations and arrhythmias.

Answer 2: Increased renin, angiotensin I, and angiotensin II and decreased aldosterone levels may be seen in primary adrenal insufficiency, in which the adrenal glands are deficient at producing aldosterone, or with ARB use due to compensatory upregulation of upstream molecules. Primary adrenal insufficiency presents with fatigue, hypotension, and salt craving; it is not caused by a medication side effect. ARBs do not cause a dry cough.

Answer 4: Increased renin and decreased angiotensin I, angiotensin II, and aldosterone levels may be seen with the use of a direct renin inhibitor, such as aliskiren. While aliskiren is occasionally used in the treatment of hypertension, it does not cause a dry cough.

Answer 5: Decreased renin, angiotensin I, angiotensin II, and aldosterone levels are not seen with any pharmacologic intervention targeting the renin-angiotensin-aldosterone pathway.

Bullet Summary:
Angiotensin-converting enzyme inhibitors block the conversion of angiotensin I to angiotensin II and cause an increase in renin and angiotensin I and a decrease in angiotensin II and aldosterone.