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You are watching: Renin hydrolyzes angiotensinogen, which is released from the _________, to form angiotensin i.

StatPearls . Sweetheart Island (FL): StatPearls Publishing; 2021 Jan-.


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Introduction

The renin–angiotensin–aldosterone system (RAAS) is a an essential regulator of blood volume and also systemic vascular resistance. While the baroreceptor reflex responds in a momentary manner to diminished arterial pressure, the RAAS is responsible for much more chronic alterations. It is created of three major compounds: renin, angiotensin II, and aldosterone. These 3 act come elevate arterial press in solution to lessened renal blood pressure, reduced salt shipment to the distal convoluted tubule, and/or beta-agonism. V these mechanisms, the body can elevate the blood push in a lengthy manner.<1><2><3>


Organ systems Involved

The RAAS entails the kidneys, lungs, systemic vasculature, and also the brain.


Function

The RAAS features to elevate blood volume and arterial ton in a prolonged manner. That does this by raising sodium reabsorption, water reabsorption, and also vascular tone.


Mechanism

Within the afferent arterioles of the kidney, specialized cells dubbed juxtaglomerular (JG) cells contain prorenin. When prorenin is secreted constitutively in the inactive form, activation that JG cells reasons the cleavage of prorenin to renin. Activation of these cells occurs in an answer to lessened blood pressure, beta-activation, or activation by macula densa cells in solution to a lessened sodium load in the distal convoluted tubule.<4><5>

Once renin has actually been released into the blood, it deserve to act top top its target, angiotensinogen. Angiotensinogen is created in the liver and is discovered continuously circulating in the plasma. Renin then acts to cleave angiotensinogen into angiotensin I. Angiotensin i is physiologically inactive, but acts together a precursor for angiotensin II.

The counter of angiotensin i to angiotensin II is catalytic analysis by one enzyme referred to as angiotensin converting enzyme (ACE). ACE is discovered primarily in the vascular endothelium the the lungs and also kidneys. ~ angiotensin i is converted to angiotensin II, the has impacts on the kidney, adrenal cortex, arterioles, and mind by binding to angiotensin II type I (AT) and form II (AT) receptors. The results discussed listed below are a result of binding to at receptors. The role of AT receptors is still being investigated, but pertinently, they have actually been presented to reason vasodilation by nitric oxide generation. In the plasma, angiotensin II has actually a half-life of 1-2 minutes, in ~ which allude peptidases degrade it into angiotensin III and IV. Angiotensin III has been displayed to have 100% that the aldosterone stimulating result of angiotensin II, yet 40% of the pressor effects, if angiotensin IV has actually further decreased the systemic effect.

In the proximal convoluted tubule of the kidney, angiotensin II action to boost Na-H exchange, boosting sodium reabsorption. Increased levels the Na in the human body acts to rise the osmolarity the the blood, resulting in a transition of liquid into the blood volume and also extracellular room (ECF). This rises the arterial pressure of the patient.

Angiotensin II also acts upon the adrenal cortex, particularly the zona glomerulosa. Here, that stimulates the release of aldosterone. Aldosterone is a steroid hormone that causes boost in salt reabsorption and also potassium excretion at the distal tubule and also collecting duct the the nephron. Aldosterone works by stimulating the insertion the luminal Na channels and also basolateral Na-K ATPase proteins. The net result is an increased level of sodium reabsorption. This has actually the same effect as mentioned previously: the increased total body salt leads to an increase in osmolarity and also subsequent rise in blood and also ECF volume. In contrast to angiotensin II, aldosterone is a steroid hormone. As a result, it enacts change by binding to nuclear receptors and also altering gene transcription. Thus, the impacts of aldosterone might take hrs to days come begin, while the results of angiotensin II are rapid.

The impact of angiotensin II on vasoconstriction takes ar in systemic arterioles. Here, angiotensin II binds to G protein-coupled receptors, bring about a an additional messenger cascade that results in potent arteriolar vasoconstriction. This acts come increase full peripheral resistance, causing rise in blood pressure.

Finally, angiotensin II acts on the brain. Here, it has actually three effects. First, it binds to the hypothalamus, stimulating thirst and also increased water intake. Second, that stimulates the release of antidiuretic hormone (ADH) by the posterior pituitary. ADH, or vasopressin, action to rise water reabsorption in the kidney by inserting aquaporin networks at the collecting duct. Finally, angiotensin II to reduce the sensitivity of the baroreceptor reflex. This diminishes baroreceptor response to an increase in blood pressure, which would be counterproductive to the goal of the RAAS.

The net result of these interactions is rise in complete body sodium, full body water, and vascular tone.


Clinical Significance

The RAAS acts to regulate blood volume and also arteriolar tone on a irreversible basis. If minor and rapid move are frequently managed via the baroreceptor reflex, the RAAS can transform blood volume chronically. Though the RAAS serves a crucial function, it can be triggered inappropriately in several problems that may then result in the advance of hypertension. For example, renal artery stenosis outcomes in a reduced volume the blood reaching one (or both) kidneys. As a result, the juxtaglomerular cell will feeling a decrease in blood volume, activating the RAAS. This have the right to lead come an inappropriate elevation of turn blood volume and arteriolar tone due to poor renal perfusion.<6><7>

Pharmacologically, the RAAS is a typically manipulated mechanism in the administration of love failure, hypertension, diabetes mellitus, and acute myocardial infarction. ACE inhibitors (e.g., enalapril), angiotensin receptor blockers (ARBs, e.g., losartan), and also aldosterone antagonists (e.g., spironolactone) all act to decrease the impact of the RAAS.

The varied mechanisms of this drugs allow their use in different scenarios. ACE inhibitors inhibit the activity of angiotensin-converting enzymes, therefore decreasing the manufacturing of angiotensin II. ARBs act to block at receptors, hence inhibiting angiotensin’s impact while preserving normal level of the compound. Aldosterone inhibitors have two particular varieties. The first (e.g., spironolactone or eplerenone) act as aldosterone antagonists. These job-related by preventing the binding that aldosterone to binding web page in the kidney, preventing insertion that Na channels. The 2nd (e.g., amiloride or triamterene) team act come block the put Na networks in the distal convoluted tubule.

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A typical use for ACE inhibitors or ARBs is in the management of hypertension. In these cases, impede or decreasing levels of angiotensin II will bring about a palliation in blood pressure. They accomplish this goal by to decrease sodium and also water reabsorption, causing a palliation in blood volume, and decreasing arteriolar tone. In addition, this drugs are frequently used in the monitoring of diabetes mellitus. Patients through diabetes mellitus often have renal manifestations such as proteinuria due to excess glucose damaging the glomerulus. Making use of ACE inhibitors or ARBs have the right to decrease efferent arteriolar tone, causing a palliation in pressure on the glomerulus. Thus, lock are typically used for prevention of worsening diabetic nephropathy.


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