A 44-year-old woman comes to the office for a follow-up appointment. Six months earlier, the patient was diagnosed with essential hypertension; she has followed dietary and exercise recommendations since then. At a follow-up visit 3 months ago, she reported episodic headaches due to migraines. Her blood pressure at that visit was 145/92 mm Hg. Antihypertensive therapy with a beta blocker was started due to its beneficial effect on migraine prophylaxis. Now, 3 months later, the patient's blood pressure has decreased to 120/80 mm Hg. She is compliant with her medication and has had no serious adverse effects. Which of the following is the most likely combination of changes in response to this patient's treatment (AT = Angiotensin) ?

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11ec160b_3c69_2da4_9249_51cbc679db87_MD0001_00 The renin-angiotensin-aldosterone system (RAAS) is the most important neurohormonal system regulating sodium/fluid balance and arterial blood pressure in the body. Regulation of the RAAS involves 3 major components: macula densa (distal tubule sodium sensor), intrarenal baroreceptors, and beta-adrenergic receptors. Beta-adrenergic regulation is mediated through sympathetic stimulation of beta-1 receptors located on juxtaglomerular cells, which stimulate the release of renin. Beta-adrenergic antagonists inhibit renin release, which in turn reduces the conversion of angiotensinogen to angiotensin I and reduces the levels of angiotensin II and aldosterone. This effect on the RAAS is only partially responsible for beta blocker effects on blood pressure, and antihypertensive efficacy of beta blockers weakly correlates with plasma renin levels. Beta blockers have no effect on ACE activity and, therefore, do not affect bradykinin levels. (Choice B) Direct renin inhibitors (aliskiren) block the conversion of angiotensinogen to angiotensin I, which leads to reduced levels of angiotensin I and II and aldosterone. Plasma renin concentration is increased via suppression of the inhibitory feedback loop. (Choices C and D) ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and lead to decreased levels of angiotensin II and aldosterone, along with increased plasma renin activity and angiotensin I levels via inhibition of negative feedback. ACE is also a kininase and normally degrades bradykinin in the body. Therefore, ACE inhibitors lead to increased levels of bradykinin, which is responsible for the coughing seen in treated patients. (Choice E) Angiotensin II receptor blockers (ARBs) block the action of angiotensin II on angiotensin (AT1) receptors, which leads to increased levels of renin and angiotensin I and II. ARBs have no effect on bradykinin levels. (Choice F) Aldosterone antagonists (spironolactone, eplerenone) compete with aldosterone for the receptor sites in the distal tubules. They raise the levels of renin, angiotensin I and II, and aldosterone via inhibition of negative feedback. Educational objective: Beta-adrenergic blocking drugs inhibit renin release by blocking beta-1 receptor-mediated regulation of the renin-angiotensin-aldosterone system. This reduces plasma renin activity, with a resulting reduction in angiotensin I, angiotensin II, and aldosterone levels. __________ References: Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. (http://www.ncbi.nlm.nih.gov/pubmed/10342782)

A 44-Year-Old Woman Comes to the Office for a Follow-Up