Angiotensin II

Through its role in the renin-angiotensin-aldosterone system (RAAS), angiotensin II regulates blood pressure, fluid balance, and vascular tone. Elevated or decreased levels of Angiotensin II may be associated with various health issues, ranging from hypertension to heart failure and kidney disease. 

Understanding how to interpret these levels may support clinicians with insights into a patient’s cardiovascular and renal conditions, allowing for more targeted and effective treatment strategies. 

What is Angiotensin II?

Angiotensin II is an essential hormone in the body’s renin-angiotensin-aldosterone system (RAAS), playing a central role in regulating blood pressure, fluid balance, and vascular tone. 

This hormone is synthesized from angiotensinogen via renin and angiotensin-converting enzyme (ACE). 

Angiotensin II acts primarily through two receptors: AT1 and AT2, influencing blood vessel constriction, fluid retention, and hormone secretion. It is essential in diagnosing and managing conditions like hypertension, heart failure, and kidney diseases and serves as a target for treatments like ACE inhibitors and angiotensin receptor blockers (ARBs).

What is the Renin-Angiotensin-Aldosterone System?

The renin-angiotensin-aldosterone system (RAAS) is a critical regulator of blood pressure, fluid balance, and vascular tone. 

The RAAS is activated when blood pressure drops or when sodium levels are low, triggering the release of renin from the kidneys. Renin then converts angiotensinogen, a protein made by the liver, into angiotensin I. 

Angiotensin I is then converted into angiotensin II by the enzyme ACE, which is primarily found in the lungs. Angiotensin II plays a central role in raising blood pressure by constricting blood vessels, stimulating the release of aldosterone (which promotes sodium and water retention), and increasing the release of vasopressin. 

These actions collectively help restore blood pressure and fluid balance. Angiotensin II's effects, mediated through receptor types AT1 and AT2, are each responsible for different physiological responses, such as vasoconstriction or vasodilation, and influencing conditions like hypertension and heart failure.

Emerging research also demonstrates that the RAAS system not only regulates blood pressure but also plays a role in organ-specific functions through autonomous, localized systems in organs like the heart and kidneys. These systems can independently manage blood flow and inflammation, contributing to conditions like heart failure. 

Who Should Get Angiotensin II Levels Tested?

Testing Angiotensin II levels can help identify and manage several health conditions. It is particularly valuable for the following groups:

Individuals with Persistent Hypertension

For patients with uncontrolled or resistant hypertension, measuring Angiotensin II levels can help determine if the RAAS is contributing to the high blood pressure. It may also be useful in diagnosing secondary hypertension, especially in cases related to renovascular conditions, where blood flow to the kidneys is compromised.

Patients with Cardiovascular Disease

Angiotensin II testing can provide important information about the risk and progression of heart failure, atherosclerosis, and myocardial infarction. Elevated levels may indicate worsening cardiovascular strain, helping clinicians decide on treatment modifications to prevent further complications.

Individuals with Renal Disorders

Angiotensin II can be a valuable marker in assessing kidney function. In conditions like chronic kidney disease (CKD) or diabetic nephropathy, testing Angiotensin II levels can help monitor disease progression and inform treatment strategies aimed at protecting renal function.

Test Preparation and Procedure

This test requires a frozen plasma sample. Venipuncture is typically required, and the laboratory company may request or require the use of a special test kit. The patient should be fasting before this test. 

Test Interpretation

Angiotensin II testing provides valuable insight into a patient's cardiovascular and renal health. However, these test results must be interpreted cautiously and in the context of the patient’s clinical presentation.

Normal Reference Ranges

Always consult the lab company used for their reference ranges. For reference, one company recommends a reference range of 0-137 pg/mL for frozen plasma samples, while another recommends a reference range of </= 52 ng/mL. 

Clinicians should consult specific lab reference ranges to ensure accurate interpretation; additionally, variations in sample handling and assay methods can influence results.

Clinical Implications of Elevated Levels

Elevated Angiotensin II levels often signal overactivation of the RAAS, which contributes to hypertension, fluid retention, and vascular remodeling. High levels are commonly seen in conditions like hyperaldosteronism, heart failure, and renovascular hypertension. 

In these cases, the body retains excessive sodium and water, increasing blood pressure and strain on the cardiovascular system. Elevated Angiotensin II also promotes tissue inflammation and fibrosis, worsening organ damage over time.

Clinical Implications of Decreased Levels

Low Angiotensin II levels can suggest angiotensin deficiency, which can lead to several health complications. These include low blood pressure (hypotension), elevated potassium levels (hyperkalemia), decreased sodium levels (hyponatremia), and increased fluid loss through urine (diuresis). 

These issues can disrupt the body's normal fluid and electrolyte balance, potentially leading to further complications if not properly managed.

The Adrenal Insufficiency-Angiotensin II Connection

In adrenal insufficiency, the connection to angiotensin II depends on whether the problem is with the adrenal glands themselves or the pituitary gland. 

In primary adrenal insufficiency, the adrenal glands don’t function properly, causing low levels of cortisol and high levels of renin (which triggers the production of angiotensin II). High angiotensin II raises blood pressure by causing blood vessels to tighten and helping the body hold onto sodium. 

In secondary adrenal insufficiency, the pituitary gland doesn’t produce enough ACTH, which tells the adrenal glands to make cortisol. Since the adrenal glands are still working, the RAAS remains normal, meaning angiotensin II levels and aldosterone stay normal, even though cortisol levels are low. 

This difference helps doctors figure out the cause of adrenal insufficiency.

Clinical Management

Elevated Angiotensin II levels often require interventions to reduce its effects on the body. Medications like ACE inhibitors and ARBs are commonly used to block Angiotensin II's action, lowering blood pressure and reducing cardiovascular strain. 

In low Angiotensin II levels, addressing the underlying cause may be necessary to restore normal blood pressure regulation.

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