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Question:

In an experiment, 3 L of isotonic saline are infused intravenously into a healthy volunteer after multiple baseline physiologic parameters are recorded.  Serial blood pressure measurements show an increase in the systolic and diastolic blood pressure.  Ultrasonography reveals an increase in the left ventricular volume and engorgement of the inferior vena cava.  Blood levels of a peptide hormone have also increased compared to baseline.  This hormone is most likely to increase which of the following in this test subject?

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Explanation:

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Intravenous infusion of isotonic saline leads to intravascular volume expansion with an increase in intracardiac volume and filling pressures.  The resultant increase in myocardial wall stretch leads to the release of endogenous natriuretic peptide hormones, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) from the atria and ventricles, respectively.

Both ANP and BNP activate guanylate cyclase, which increases intracellular cyclic GMP, and leads to downstream physiologic effects in various tissues.  In the kidney, natriuretic peptides promote afferent glomerular arteriolar vasodilation and efferent arteriolar constriction, causing increased glomerular filtration rate; this leads to increased natriuresis (sodium excretion) and diuresis (fluid excretion).  Natriuretic peptides also directly inhibit proximal tubular sodium reabsorption and renin secretion.  Decreased renin secretion results in reduced angiotensin II and aldosterone levels, further promoting natriuresis and diuresis.

(Choice A)  An increase in aldosterone levels causes sodium and water retention, hypokalemia, and metabolic alkalosis due to increased urinary hydrogen excretion.  Infusion of isotonic saline inhibits aldosterone release and causes a decrease in urinary hydrogen excretion and acid content of the urine.

(Choice C)  Activation of the renin-angiotensin-aldosterone system (eg, hypotension, hypovolemia, increased sympathetic activity) leads to an increase in renin secretion, which in turn leads to increased production of angiotensin II and aldosterone.  Angiotensin II increases sodium reabsorption in the proximal tubules and stimulates aldosterone secretion from the adrenal cortex, which in turn promotes sodium and water reabsorption in the distal tubule.  An increase in intravascular volume by isotonic saline inhibits renin release and causes a decrease in sodium and water reabsorption.

(Choice D)  Infusion of isotonic saline inhibits the release of antidiuretic hormone (vasopressin), reducing renal water reabsorption in the collecting duct.

(Choice E)  Angiotensin II causes arteriolar vasoconstriction via direct actions on AT1 receptors on the cell membrane.  Infusion of isotonic saline decreases renin release with a reduction in angiotensin II production, resulting in decreased systemic vascular resistance.

Educational objective:
Atrial natriuretic peptide and brain natriuretic peptide are released from the atria and ventricles, respectively, in response to myocardial wall stretch due to intravascular volume expansion.  These endogenous hormones promote increased glomerular filtration rate, natriuresis, and diuresis.