What Is the Renin-Angiotensin System?

The renin-angiotensin system (RAS) is a hormone system in the human body that is mainly known for regulating blood pressure (BP) and fluid volume. It is named for its two central agents, renin and angiotensin. The renin-angiotensin system is also known as renin-angiotensin-aldosterone system (RAAS) due to a third major participant in this system called aldosterone. The level of activity of the renin-angiotensin system determines and is determined by the body’s BP level.

When the BP in a person drops or is low, the renin-angiotensin system is activated. Low BP is clinically known as hypotension. The kidney, through its secretory granule-containing cells called juxtaglomerular cells, releases renin. This type of enzyme is also released when there is low blood volume, activity in the sympathetic nervous system, or when the macula densa cells of the juxtaglomerular apparatus detect a decrease in sodium chloride levels.

Renin then splits apart a globular protein that is released from the liver called angiotensinogen. This cleaving process converts angiotensinogen into angiotensin I. This substance is classified as a decapeptide, which means that it consists of a ten-amino acid chain. For its role in this process, angiotensinogen is also known as the angiotensin precursor.

Angiotensin I by itself, however, is inactive. This changes when it reacts with another enzyme that is produced from the lungs’ vascular endothelium, a thin layer of flat cells that lines the organ’s capillaries. It is known as the angiotensin-converting enzyme (ACE) and is responsible for turning angiotensin I into angiotensin II, the active form of this particular peptide. It does so by taking off two of its terminal residues.

As an active peptide, angiotensin II constricts the blood vessels, a process known as vasoconstriction. The narrowed passageways thus lead to restrained blood flow and, consequently, a rise in BP, known clinically as hypertension. Moreover, angiotensin II activates the release of the hormone aldosterone from the kidney’s juxtaglomerular cells. Aldosterone causes the reabsorption of water and sodium in the kidney, thus leading to an increase in blood volume, and, by extension, BP.

The pharmaceutical industry has reacted by introducing three classes of drugs. They were created to lessen or regulate the activity of the renin-angiotensin system. Renin inhibitors, or blockers, are designed to suppress renin from transforming angiotensinogen to angiotensin I. ACE inhibitors are meant for the next step, inhibiting the conversion of angiotensin I to angiotensin II. Finally, there are the angiotensin II receptor antagonists—also know angiotensin receptor blockers (ARBs)—which block the activation of angiotensin II.