Renin-angiotensin system

Overview
The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.

Activation
The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in a hemorrhage).


 * 1) If the perfusion of the juxtaglomerular apparatus in the kidneys decreases, then the juxtaglomerular cells release the enzyme renin.
 * 2) Renin cleaves an inactive peptide called angiotensinogen, 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 system. Angiotensin II acts as an  endocrine,  autocrine/ paracrine, and intracrine hormone.



Effects
Angiotensin I may have some minor activity, but angiotensin II is more potent. Angiotensin II has a variety of effects on the body:
 * Throughout the body, it is a potent vasoconstrictor.
 * In the kidneys, it constricts glomerular arterioles, having a greater effect on efferent arterioles than afferent. As with most other capillary beds in the body, the constriction of afferent arterioles increases the arterioler resistance, raising systemic arterial blood pressure and decreasing the blood flow. However, the kidneys must continue to filter enough blood despite this drop in blood flow, necessitating mechanisms to keep glomerular blood pressure up. To do this, Angiotensin II constricts efferent arterioles, 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.
 * In the adrenal cortex, it acts to cause the release of aldosterone. Aldosterone acts on the tubules (i.e. the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. Potassium is secreted into the tubule in exchange for the sodium, which is reabsorbed. Aldosterone also acts on the central nervous system to increase a person's appetite for salt, and to make them feel thirsty.
 * ''Release of Anti Diuretic Hormone (ADH) -- also called vasopressin -- ADH is made in the hypothalamus. ADH is stored and released from the pituitary gland.

These effects directly act to increase the amount of fluid in the blood, making up for a loss in volume, and to increase blood pressure.

Clinical significance
The renin-angiotensin system is often manipulated clinically to treat high blood pressure.
 * Inhibitors of angiotensin-converting enzyme (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II. Captopril is an example of an ACE inhibitor.
 * Alternatively, angiotensin receptor blockers (ARBs) can be used to prevent angiotensin II from acting on angiotensin receptors.
 * A new drug called Aliskiren is being released in 2007 which directly inhibits renin.

Other uses of ACE
Interestingly, ACE cleaves a number of other peptides, and in this capacity is an important regulator of the kinin-kallikrein system.

Fetal renin-angiotensin system
In the fetus, the renin-angiotensin system is predominantly a sodium-losing system, as angiotensin II has little or no effect on aldosterone levels. Renin levels are high in the fetus, while angiotensin II levels are significantly lower &mdash; this is due to the limited pulmonary blood flow, preventing ACE (found predominantly in the pulmonary circulation) from having its maximum effect.