Renin-Angiotensin System and its Role in the Regulation of Blood Pressure

There are three classes of blood pressure lowering drugs (anti-hypertensives), ACE Inhibitors, Renin Inhibitors and Angiotensin Receptor Inhibitors, that exert their effects via the Renin-Angiotensin system. (Renin is not the same as rennin (with 2 n’s in the middle) which is found in rennet and is used to form curds in milk, which is utilized in cheese making.)

The system is sometimes called the Renin-Angiotensin-Aldosterone system (RAAS).

How the renin-angiotensin system works

The renin-angiotensin system controls blood pressure by a number of mechanisms including regulation of contraction of blood vessels.

The constriction of blood vessels makes the inside narrower and this causes blood pressure to increase. Think of a blood vessel as being like a hose. If you squeeze the end of a hose to make it narrower, the water will come out with higher pressure. It works the same way with blood vessels; where they are constricted (squeezed) the pressure increases.

The system also controls the amount of fluid in the blood, so the volume of the blood is increased.

 - When the body wants to increase blood pressure it activates the renin-angiotensin system. When decreased blood pressure is required, the renin-angiotensin system in down regulated. -

Overview of the role of angiotensin II in blood pressure

In the blood, a small protein called angiotensin II (roman numeral 2, not 11) makes blood vessels constrict. This protein is made by a cascade of events. As the level of angiotensin II in the blood increases the blood vessels become more constricted.

Angiotensin II, by acting on the kidneys and adrenal cortex, reduces the volume of urine. Less urine means that more water is retained by the body, which increases the amount of fluid (volume) of the blood, which further increases blood pressure.

The first precursor is called angiotensinogen. This protein is made mainly by the liver, and then released into the blood.

Renin, an enzyme released from the kidneys, breaks the angiotensinogen into pieces. One piece is called angiotensin I. Another enzyme in the blood called angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, by removing a small piece from the end of the angiotensin I.

Angiotensin II regulation of blood pressure

The amount of angiotensin II in the blood is regulated in two ways. First, the body controls the blood levels of the precursor protein angiotensinogen, and second, regulates the activity levels of the enzymes (renin and angiotensin converting enzyme) that convert one protein to another.

Contraction of blood vessels

Only angiotensin II causes constriction of blood vessels. Angiotensinogen and angiotensin I do not cause blood vessels to constrict. Angiotensin II binds to angiotensin receptors that are found on smooth muscle cells. These cells form a layer of the walls of blood vessels. The binding of angiotensin II to the angiotensin receptors on the surface of the smooth muscle cells signals the smooth muscle cells to contract, which makes the blood vessel contract.

When the blood vessel walls are contracted more, blood pressure will go up. When there is less angiotensin II, the blood vessels walls will relax and blood pressure will drop.

Volume of the blood

Angiotensin II, also, plays a role in the both the volume of urine and the amount of sodium (salt) in the urine. The higher the level of angiotensin II, the less the volume of urine, the more fluid in the body and the higher the volume of blood. As the volume of blood increases, this increases blood pressure.

A decrease in the volume of urine is due to angiotensin II acting directly on the kidney, and indirectly on the adrenal cortex (on the adrenal glands). Angiotensin II causes the adrenal cortex to release a compound called aldosterone which also acts on the kidney to decease the volume and sodium content of the urine. In even more of a double whammy for those with high blood pressure, aldosterone also works on the nervous system to increase the appetite for salt and the feeling of thirst.

Drugs that affect the renin-angiotensin system

Blood pressure lowering drugs that work on the renin-angiotensin system, do so directly or indirectly, by either reducing the amount of angiotensin II in the blood or by stopping some of the angiotensin II binding to walls of blood vessels. These drugs cause blood vessels to be less constricted (more relaxed), and increases the volume of the urine and so decreases the volume of blood in the body.both of these effects lower blood pressure..

ACE inhibitors and Renin inhibitors both interfere with steps of the renin-angotensin system, with the result that there is less angiotensin II in the blood, and so the blood vessels will be less constricted. Renin inhibitors inhibit the enzyme renin, which results in angiotensinogen not being broken into pieces, so angiotensin I is not made. ACE inhibitors block the action of ACE (angiotensin converting enzyme), so angiotensin I is not converted angiotensin II. Angiotensin Receptor inhibitors will stop some of the angiotensin II binding to the receptors on the smooth muscle cells, which means that the blood vessels will be more relaxed. The net result of all these drugs is a lowering of blood pressure. How much blood pressure is lowered with any of these drugs depends on the individual and the dose .