A 60-year-old man comes to the office for a routine follow-up visit. He feels well overall except for an intermittent, mild, generalized headache. The patient has no known medical problems and takes no medications. He does not smoke, follows a generally healthy diet, and exercises daily. On examination, his blood pressure is 150/85 mm Hg, and he is started on lisinopril. At a follow-up visit, the patient's blood pressure is 128/78 mm Hg. He also has a dry cough that began a few weeks after starting lisinopril. This drug is stopped and losartan is now prescribed. The patient seems to be compliant with his medication; the cough resolves and he experiences no significant side effects. When compared with no treatment at all, this patient's current therapy is most likely to result in which of the following changes?

Question

Quizplus · Accepted Answer

11ec160b_3b76_1b75_9249_570528edf7ee_MD0001_00 The renin-angiotensin-aldosterone system (RAAS) regulates arterial blood pressure and extracellular fluid balance. Renin release is stimulated by decreased sodium delivery to the distal tubule, low blood pressure (eg, low intravascular volume), and β1 sympathetic activity. Renin converts angiotensinogen to angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), which also degrades bradykinin. Angiotensin II stimulates the type 1 angiotensin II receptors found on vascular smooth muscle (causing vasoconstriction) and the adrenal cortex (stimulating aldosterone secretion). Systemic vasoconstriction and increased aldosterone-induced sodium reabsorption raise blood pressure, inhibiting further renin release from the kidneys (negative feedback). Angiotensin II receptor blockers (ARBs) such as losartan competitively bind to angiotensin II receptors and block the effects of angiotensin II, resulting in vascular smooth muscle relaxation and decreased aldosterone secretion. This reduces blood pressure, stimulating renal renin production, which in turn increases conversion of angiotensin I to angiotensin II. Because ACE function remains intact with the use of ARBs, bradykinin levels are not significantly affected. This is in contrast to ACE inhibitors, which lower angiotensin II and aldosterone levels but increase bradykinin levels (Choice C). Bradykinin is thought to increase prostaglandin production, which induces coughing due to bronchial irritation. (Choice A) β1 adrenergic blockers would inhibit renin release from the juxtaglomerular apparatus, thereby suppressing the entire renin-angiotensin cascade (although lowering of the blood pressure would somewhat blunt this response). ACE activity is not regulated by renin, and so bradykinin levels are unchanged. (Choice B) Direct renin inhibitors reduce plasma renin activity, which reduces levels of all downstream hormones. Suppression of the whole cascade lowers blood pressure, which would stimulate increased renin production. Plasma renin activity, however, is inhibited. (Choice E) This combination of changes is seen with mineralocorticoid receptor antagonist (eg, spironolactone) or diuretic use. Mineralocorticoid receptor antagonists block aldosterone activity by binding to the mineralocorticoid receptor. Diuretics would cause a fall in blood pressure, stimulating the RAAS and increasing blood levels of all hormones. Educational objective: Angiotensin II receptor blockers (ARBs) work by blocking angiotensin II type 1 receptors, inhibiting the effects of angiotensin II. This results in arterial vasodilation and decreased aldosterone secretion. The resulting fall in blood pressure increases renin, angiotensin I, and angiotensin II levels. ARBs do not affect the activity of angiotensin-converting enzyme, and therefore they do not affect bradykinin degradation and do not cause cough. __________ References: Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients. (http://www.ncbi.nlm.nih.gov/pubmed/7843751) Effects of losartan on the renin-angiotensin-aldosterone axis in essential hypertension. (http://www.ncbi.nlm.nih.gov/pubmed/7595905) The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. (http://www.ncbi.nlm.nih.gov/pubmed/17970613)

A 60-Year-Old Man Comes to the Office for a Routine