What Is the Renin-Angiotensin System? (text)

What Is the Renin-Angiotensin System?
The Importance of the Kidneys in Regulating Long-Term Blood Pressure

From Craig Weber, M.D., About.com Guide


The renin-angiotensin system is a group of related hormones that act together to regulate blood pressure. It is called a system because each part influences the other parts and all are necessary for the whole to function correctly. The renin-angiotensin system, working together with the kidneys, is the body's most important long-term blood pressure regulation system. While short-term blood pressure changes are caused by a variety of factors, almost all long-term blood pressure adjustments are the responsibility of the kidneys and the renin-angiotensin system.
How Does the Renin-Angiotensin System Work?

The important members of the renin-angiotensin system are:

* Renin
* Angiotensin I
* Angiotensin II
* Angiotensin Converting Enzyme

When the blood pressure drops for any reason, special cells in the kidney detect the change and release renin into the blood stream. Renin by itself does not really affect the blood pressure. Instead, it floats around and converts inactive forms of angiotensin into angiotensin I. These inactive forms of angiotensin, which are produced by the liver, are not able to alter the blood pressure until renin changes them into angiotensin I.

Angiotensin I is able to alter the blood pressure to some degree, but it isn't strong enough to cause large changes. Instead, most angiotensin I is converted to angiotensin II, a much more powerful hormone that does cause large changes in blood pressure. This second conversion happens mainly in the lungs via the action of another molecule called angiotensin converting enzyme (ACE). (This conversion is shut down by drugs called ACE Inhibitors, an important type of high blood pressure medication.)

Angiotensin II is a strong hormone, and can act directly on blood vessels to cause blood pressure increases. It also has another even more important function - stimulating the release of aldosterone. Aldosterone is a very powerful vasoconstrictor that causes large increases in blood pressure, but is more important because it can actually change the baseline filtering activity of the kidneys. Aldosterone causes the kidneys to retain both salt and water, which - over time - increases the amount of water in the body. This increase, in turn, raises blood pressure.

Angiotensin I, angiotensin II, and aldosterone do not live forever in the blood. Instead, they exist for a period of time and are then broken down by other molecules. The renin-angiotensin system, as a whole, responds to both short-term and long-term variations in blood pressure. It is activated by sudden drops in blood pressure - such as those that occur after blood loss - but is also stimulated by smaller, less dramatic blood pressure fluctuations.

As a long-term regulator of blood pressure, the renin-angiotensin system has a constant baseline level of activity, and actually works much like the gas pedal of a car. Constant pressure on the gas pedal is required to keep the car moving forward, even when you just want to go the same speed. If you need to, though, you can press the pedal down suddenly in order to quickly speed up. Likewise, constant activity in the renin-angiotensin system keeps blood pressure steady over the long term, but sudden bursts of action are possible when quick response is required.
Why Is the Renin-Angiotensin System Important for High Blood Pressure?

Scientific papers, conference presentations, and even entire textbooks have been written about the importance of the renin-angiotensin system in blood pressure regulation. This is an intense area of research that is being pursued by some of the most talented scientists in the world. The renin-angiotensin system gets so much attention because it is known to be an important factor that could help us understand:

* Why people develop high blood pressure at all
* Why some people don't respond well to normal high blood pressure treatment
* Why some people with high blood pressure develop more complications than others

For example, doctors know that treating African-American patients with ACE inhibitors doesn't usually work as well as treating them with other medicines, even though ACE inhibitors are very effective in other ethnic groups. This is likely because African-Americans have a different level of activity in their renin-angiotensin system, which makes them less sensitive to drugs that work by blocking the system.

A number of effective high blood pressure treatments have been developed as a direct result of our understanding of the renin-angiotensin system. Along with ACE inhibitors, which stop the conversion of angiotensin I to angiotensin II, other drugs work by targeting different parts of the system. Angiotensin receptor blockers (ARBs), for example, prevent angiotensin I and angiotensin II from binding to blood vessels and causing vasoconstriction.

While the fine details of the renin-angiotensin system are still being discovered, our understanding of this important regulatory mechanism has already led to the development of several high blood pressure treatments and a better understanding of how to manage high blood pressure over the long term.

Sources:

1. Rose, BD, Post, TW, Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York, 2001
2. Hall JE, Guyton AC, Jackson TE, et al. Control of glomerular filtration rate by renin-angiotensin system. Am J Physiol 1977; 233:F366.
3. Toffelmire EB, Slater K, Corvol P, et al. Response of prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay. J Clin Invest 1989; 83:679.