Renin Angiotensin Aldosterone System (RAAS)

Renin Angiotensin Aldosterone System (RAAS)

The renin angiotensin aldosterone system (RAAS) is a hormone system that regulates blood pressure and fluid balance. The juxtaglomerular cells are a group of baroreceptors located in the afferent arterioles of the kidney, which can sense if the blood volume is low, these cells will then secrete renin directly into circulation. Plasma renin then converts angiotensinogen released by the liver to angiotensin I. Angiotensin I is then converted to angiotensin II in the lungs by an enzyme called, angiotensin converting enzyme or ACE. Angiotensin II is a strong vasoactive peptide that causes blood vessels to constrict leading to increased blood pressure, and it mainly works on the efferent arterioles of the kidney. Angiotensin II also stimulates the secretion of the hormone aldosterone from the zona glomerulosa in the adrenal cortex. Aldosterone then acts on the distal convoluted tubules and the cortical collecting ducts of the kidneys, increasing the reabsorption of sodium and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure.

If the renin–angiotensin–aldosterone system is abnormally active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure (e.g. ACE inhibitors). These drugs are one of the main ways to control high blood pressure (hypertension), congestive heart failure, kidney failure, and harmful effects of diabetes on the blood vessels and the kidneys.

Activation of Renin Angiotensin Aldosterone System:

The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in hemorrhage). This loss of pressure is sensed by baroreceptors in the carotid sinus. However, in an alternative fashion, a decrease in the filtrate NaCl  (sodium chloride) concentration and/or decreased filtration rate will stimulate the macula densa to signal the juxtaglomerular cells located in the afferent arterioles to release renin.

1. If the perfusion of the juxtaglomerular apparatus in the kidney’s macula densa decreases, then the juxtaglomerular cells release the enzyme renin.
2. Renin cleaves angiotensinogen, which is a zymogen, converting it into angiotensin I.
3. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), which is found mainly in lung capillaries.
4. Angiotensin II is the major bioactive product of the renin angiotensin aldosterone system, which is a very strong vasoconstrictor. Angiotensin II also leads to the release of aldosterone from the zona glomerulosa in the adrenal cortex.

Effects of Renin Angiotensin Aldosterone System on the Cardiovascular system:

It is believed that angiotensin I may have some minor activity, but angiotensin II is the major bio-active product. Angiotensin II has a variety of effects on the body:

• Throughout the body, it is a potent vasoconstrictor of arterioles.
• In the kidneys, it constricts glomerular arterioles, having a greater effect on efferent arterioles than afferent, raising systemic arterial blood pressure and decreasing the blood flow which forces blood to build up in the glomerulus, increasing glomerular pressure. The glomerular filtration rate (GFR) is thus maintained, and blood filtration can continue despite lowered overall kidney blood flow.
• Angiotensin II stimulates the hypertrophy of renal tubule cells, leading to further sodium reabsorption.
• In the adrenal cortex, it acts to cause the release of aldosterone. Aldosterone acts on the tubules (e.g., the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. This increases blood volume and, therefore, increases blood pressure. In exchange for the reabsorbing of sodium to blood, potassium is secreted into the tubules, becomes part of urine and is excreted.
• Release of anti-diuretic hormone (ADH), also called vasopressin – ADH is made in the hypothalamus and released from the posterior pituitary gland. As its name suggests, it also exhibits vaso-constrictive properties, but its main course of action is to stimulate reabsorption of water in the kidneys. ADH also acts on the central nervous system to increase an individual’s appetite for salt, and to stimulate the sensation of thirst.

Clinical Significance of Renin Angiotensin Aldosterone System:

• Inhibitors of angiotensin-converting enzyme are often used to reduce the formation of the more potent angiotensin II. Captopril is an example of an ACE inhibitor. ACE cleaves a number of other peptides, and in this capacity is an important regulator of the kinin–kallikrein system, as such blocking ACE can lead to side effects.
• Angiotensin receptor blockers (ARBs) can be used to prevent angiotensin II from acting on angiotensin receptors.
• Direct renin inhibitors can also be used for hypertension. The drugs that inhibit renin are aliskiren and the investigational remikiren.

These effects directly act in concert to increase blood pressure.

This video tutorial is brought to you by: Ali Feili, M.B.A., M.D.