A 44-year-old man comes to the office due to increasing shortness of breath. While climbing the stairs to his second-floor apartment, the patient must now stop halfway to catch his breath. He has a history of nonischemic cardiomyopathy and chronic heart failure with reduced ejection fraction. After evaluation, treatment with a new medication is begun that improves his symptoms by increasing urine output and decreasing peripheral vascular resistance. The medication works by inhibiting a metalloprotease to prolong the action of endogenous polypeptides. These polypeptides are most likely secreted by which of the following cell types?

Question

A 44-year-old man comes to the office due to increasing shortness of breath.  While climbing the stairs to his second-floor apartment, the patient must now stop halfway to catch his breath.  He has a history of nonischemic cardiomyopathy and chronic heart failure with reduced ejection fraction.  After evaluation, treatment with a new medication is begun that improves his symptoms by increasing urine output and decreasing peripheral vascular resistance.  The medication works by inhibiting a metalloprotease to prolong the action of endogenous polypeptides.  These polypeptides are most likely secreted by which of the following cell types?

Quizplus · Accepted Answer

11ec160b_3c8f_5398_9249_b54c720e3fa1_MD0001_00 In response to myocardial stretching due to volume overload, atrial and ventricular cardiomyocytes secrete atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). These peptides are subsequently broken down and inactivated by the metalloprotease neprilysin. This patient with chronic heart failure was most likely given a neprilysin inhibitor (eg, sacubitril), allowing for enhanced activity of ANP and BNP. Once secreted, ANP and BNP bind to natriuretic peptide receptors to activate guanylate cyclase and form cyclic GMP, which stimulates diuresis and peripheral vasodilation to help alleviate volume overload. Several organs and tissues are affected as follows: (Choice C) Hepatic stellate cells (perisinusoidal cells of Ito) may help regulate hepatic blood flow via release of local mediators; however, these cells do not play a significant role in heart failure. (Choice D) Myocardial Purkinje fibers facilitate the organized transport of electrical impulses from the sinoatrial node through the atria, atrioventricular node, and ventricles; however, these fibers are not known to have endocrine function. (Choice F) Vascular endothelial cells regulate systemic blood flow via release of vasodilators, such as nitric oxide and prostacyclin, and vasoconstrictors, such as endothelin and thromboxane A2. However, these local mediators are not a significant target of therapy for chronic heart failure. Educational objective: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted by atrial and ventricular cardiomyocytes in response to myocardial stretching induced by hypervolemia. These natriuretic peptides inhibit the renin-angiotensin-aldosterone system and stimulate peripheral vasodilation and increased urinary excretion of sodium and water. Neprilysin inhibitors (eg, sacubitril) prevent the degradation of ANP and BNP, enhancing their beneficial effects in heart failure. __________ References: The natriuretic peptide system in the pathophysiology of heart failure: from molecular basis to treatment. (http://www.ncbi.nlm.nih.gov/pubmed/26637405)

A 44-Year-Old Man Comes to the Office Due to Increasing