Role of the renin-angiotensin system

The renin-angiotensin system (RAS) is an important hormone system that regulates blood pressure, fluid and electrolyte balance, and processes involved in tissue renovation. It has also been implicated in the development of fibrosis.

In the RAS cascade, the hormone angiotensinogen is converted to angiotensin I by the enzyme renin, and angiotensin I is then converted to the powerful vasoconstrictor angiotensin II by angiotensin-converting enzyme (ACE). This enzyme is found on the surface of endothelial cells in blood vessels.

Angiotensin II, a key component of the RAS system, binds to two receptors: the angiotensin-1 receptor (AT-1) and the angiotensin-2 (AT-2) receptor.

The AT-1 receptor mediates the classical actions of angiotensin II, including constriction of blood vessels, sodium retention, and cell growth. However, one consequence of AT-1 receptor activation is an increase in fibroblasts, resulting in fibrosis. Conversely, AT-2 receptor activation promotes dilatation of blood vessels, inhibition of cell growth and cell death, and is considered to play a beneficial regulatory role to the effects of AT-1 receptor activation.