View source for WBR0738

 {{WBRQuestion
|QuestionAuthor= {{YD}} (Reviewed by  {{YD}})
|ExamType=USMLE Step 1
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|MainCategory=Physiology
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|MainCategory=Physiology
|MainCategory=Physiology
|SubCategory=Endocrine, Renal
|Prompt=A researcher is studying the effect of a new medication, MedX. He uses mice to conduct his experiments. Following the intravenous administration of MedX, the researcher notes a decreased secretion of aldosterone secondary to MedX's effect in reducing the production of a compound from the pulmonary vasculature. Based on the image below, which of the following reactions is most likely the first to be inhibited upon administration of MedX?

[[Image:WBR RAAS pathway.png|700px]]
|Explanation=The [[renin-angiotensin aldosterone system]] ([[RAAS]]) is a major hormonal pathway that plays a significant role in the control of arterial blood pressure, tissue perfusion, and extracellular volume. The RAAS pathway begins by the expression and secretion of [[renin]], the rate-limiting enzyme of the RAAS pathway. Renin is mainly synthesized and stored in the juxtraglomerular (JG) apparatus, which lines the afferent arteriole of the renal [[glomerulus]] and is composed of JG cells and [[macula densa]]. 

Renin cleaves the N-terminal portion of [[angiotensinogen]], a compound that is mainly expressed by the liver at a stable rate. Angiotensinogen cleavage results in the formation of [[angiotensin I]], a biologically inert decapeptide. Angiotensin I is hydrolyzed by angiotensin-converting enzyme ([[ACE]]) or kininase II, an enzyme on plasma membranes of endothelial cells, neuroepithelial cells, and renal proximal tubule cells. ACE acts by removing the C-terminal dipeptide to form angiotensin II, an octapeptide. Also, ACE has a role in metabolizing [[bradykinin]] and [[kallidin]], which are important vasodilator peptides. Unlike angiotensin I, angiotensin II is an active potent vasoconstrictor. Angiotensin II is the primary effector of numerous actions.

The effects of MedX are similar to angiotensin-converting enzyme (ACE) inhibitors. ACE is synthesized in various cells, including the endothelial cells of the pulmonary vasculature. ACE converts angiotensin I to angiotensin II. The inhibition of the ACE leads to the inhibition of the entire renin-angiotensin pathway and the deficient production of aldosterone.
|AnswerA=A
|AnswerAExp=Angiotensinogen is formed by the liver. It is converted to angiotensin I by renin. Renin is synthesized and stored in the juxtraglomerular apparatus of the kidney.
|AnswerB=B
|AnswerBExp=Angiotensin-converting enzyme (ACE) is synthesized in various cells, including the endothelial cells of the pulmonary vasculature. ACE converts angiotensin I to angiotensin II.
|AnswerC=C
|AnswerCExp=ACE does not act at this level of the pathway.
|AnswerD=D
|AnswerDExp=ACE does not act at this level of the pathway.
|AnswerE=E
|AnswerEExp=ACE does not act at this level of the pathway.
|EducationalObjectives=Angiotensin-converting enzyme (ACE) is synthesized in various cells, including the endothelial cells of the pulmonary vasculature. ACE converts angiotensin I to angiotensin II.
|References=Atlas SA, The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13(8):S9-20.<br>
Karlberg BE. Cough and inhibition of the renin-angiotensin system. J Hypertens Suppl. 1993;11(3):S49-S52.<br>
First Aid 2014 page 530
|RightAnswer=B
|WBRKeyword=Angiotensin, Converting, Enzyme, ACE, Inhibitor, ACE inhibitor, Angiotensinogen, Renin, Pulmonary, Vasculature, Hormone, Conversion, Angiotensin I, Angiotensin II, Angiotensin 1, Angiotensin 2, Aldosterone
|Approved=Yes
}}