The renin-angiotensin-aldosterone system controls salt and water balance in the human body and also regulates blood pressure to a certain extent. Various organs, hormones, and enzymes are involved in this regulatory circuit.
What is the renin-angiotensin-aldosterone system?
The lungs, liver, and kidneys are involved in the regulatory circuit of the renin-angiotensin-aldosterone system. Water and salt balance are regulated by this system, and blood pressure is also indirectly affected. The renin-angiotensin-aldosterone system (RAAS) is a cascade that regulates water and salt balance in humans. It also indirectly influences blood pressure. The lungs, liver and kidneys are involved in the control loop of the renin-angiotensin-aldosterone system. Disturbances in the renin-angiotensin-aldosterone system can result in high blood pressure. Various drugs used to regulate blood pressure also act on the RAAS. At the beginning of the regulatory circuit is the hormone-like enzyme renin. This is formed in the kidney. Renin cleaves the prohormone angiotensinogen into angiotensin I. Angiotensinogen is synthesized in the liver. Angiotensin I is in turn converted to angiotensin II by angiotensin converting enzyme (ACE), which is produced in the lungs. Angiotensin II acts on various target structures. It also causes secretion of the hormone aldosterone.
Function and role
The hormone renin is produced in the juxtaglomerular apparatus of the kidneys. This structure consists of various specialized cells and measures, on the one hand, blood pressure within certain vessels of the renal corpuscles and, on the other hand, the salt content in the urine in the urinary tubules. The juxtaglomerular apparatus also responds to information from the autonomic nervous system and to various hormones. Decreased blood flow to the renal corpuscle results in increased release of renin. Reduced blood pressure in the renal corpuscles, a lowered concentration of sodium chloride in the urine and activation of the sympathetic nervous system also result in increased release of renin. Renin acts as a protein-splitting enzyme in the body. In this way, it can turn angiotensinogen into angiotensin I. This in turn is converted into angiotensin II. Angiotensin II initially causes the small blood vessels (capillaries and arterioles) to contract. This vasoconstriction immediately increases blood pressure. In the kidney, too, angiotensin II results in a constriction of the blood vessels. In particular, the vessels leading away from the renal corpuscles are affected. This increases blood pressure and vascular resistance within the renal corpuscles. The purpose of this mechanism is to maintain the filtration capacity of the kidneys even when renal blood flow is reduced. Angiotensin II also acts on the adrenal gland. It stimulates the adrenal gland to secrete the hormone aldosterone. Aldosterone leads to an increased return of sodium from the urine into the blood in the kidney. Sodium always draws water with it, so that not only the saline content of the blood increases, but also the blood volume. As a result, blood pressure also increases. In the pituitary gland, angiotensin II causes the release of antidiuretic hormone (ADH). This is also known as vasopressin because of its vasoconstrictor effect. However, it leads not only to vasoconstriction but also to a reduced excretion of water via the urine. The result is again an increase in blood pressure. In the central nervous system (CNS), the various hormones trigger a hunger for salt and a feeling of thirst. All mechanisms together therefore lead to an increase in salt and water content in the body. This increases blood volume and ultimately blood pressure. The renin-angiotensin-aldosterone system is regulated via a negative feedback loop. High blood pressure and higher levels of angiotensin II and aldosterone inhibit the release of renin and thus also prevent the cascade.
Diseases and medical conditions
The renin-angiotensin-aldosterone system acquires pathologic significance in renal artery stenosis, in heart failure, or in advanced liver disease. In renal artery stenosis, narrowing of the renal artery occurs. In most cases, this narrowing is caused by arteriosclerosis. In the context of this stenosis, drastic increases in blood pressure occur. This is also referred to as renal hypertension.The cause of this high blood pressure is the so-called Goldblatt mechanism. When blood flow to the kidney is reduced, increased renin is released. This leads to activation of the renin-angiotensin-aldosterone system. As a result, blood pressure increases, but blood cannot reach the renal vessels due to stenosis. Consequently, renin continues to be released because the juxtaglomerular apparatus within the kidneys still measures blood pressure that is too low. The remaining vessels of the body suffer from the pressure load. Renal hypertension usually occurs when more than 75% of the arterial diameter is occluded by the stenosis. In heart failure and also in liver cirrhosis, hypovolemia occurs in later stages. Again, activation of the renin-angiotensin-aldosterone system raises blood pressure. Temporarily, this leads to success. In the longer term, however, the increase in blood pressure leads to stress and damages the organs. Since the renin-angiotensin-aldosterone system plays an important role in regulating blood pressure, it is also the target of many drugs for high blood pressure. The well-known ACE inhibitors inhibit the angiotensin converting enzyme (ACE). This prevents the formation of angiotensin II. The cascae thus ends abruptly, and there is no increase in blood pressure. Alternatively, the effect of angiotensin II can be blocked with blood pressure medications. So-called angiotensin receptor blockers or AT1 antagonists are used for this purpose. Renin inhibitors, on the other hand, directly inhibit the release of renin. This stops the entire control loop before it even starts. Aldosterone antagonists inhibit the release of antidiuretic hormone and the hormone aldosterone. This is another way to lower high blood pressure.
