Vasoconstriction due to Angiotensin II
If you want to know ALL about angiotensin, you would have to lock yourself in a science library and study for weeks and weeks. Then you would find that some things are not always what they seem, but at least you could hit the high spots!!
Just to be sure we are all together on this, please go back to the previous page. As Angiotensin II is such an important substance we must remember how it is generated and now we must follow its reactions throughout the body. And I can tell you that there are surprises in store!Note that Angiotensinogen (the source of angiotensin) is a serum protein acted on by renin whose source is the kidney. Angiotensinogen was pictured as a bunch of grapes whose “stem”, the future Angiotensin I was removed by the renin.
Here is a little more about that “stem”: The building blocks of all proteins are amino acids and as we would expect, the “stem” contains a chain of amino acids, 14 in all. When renin removes the chain, it removes an additional four amino acids leaving Angiotensin I with only 10. Angiotensin I has little activity and must be “activated” or “converted” to the active form. The enzyme carrying out this task is ACE – the angiotensin converting enzyme - most of the “conversion” taking place in the lungs. Check out the last page again.
This “conversion” is relatively simple because ACE merely snips off another two amino acids from the Angiotensin I and this leaves a chain of only 8 - the active Angiotensin II. (If we just say “angiotensin” it is assumed that we mean Angiotensin II.)
If you take a solution of angiotensin and inject it into a person's vein, an immediate rise in blood pressure occurs. If you inject the angiotensin into a patient with untreated Bartter's syndrome the rise in blood pressure is much less. This is because the blood is already overloaded with angiotensin. In Bartter's, angiotensin is being made greatly in excess of demand. We also know this because we can observe the changes in the adrenal glands. These changes will be described later.
In the course of research, it was found that the angiotensin molecule generally did not act directly on an artery but had to work through a receptor. It was soon found that there were two receptors that were named AT1 and AT2. To this day, nobody knows for sure just what the AT2 receptor is doing so you can forget about it. AT1 is the main receptor for Angiotensin II.
It was next found that if a person had hypertension and the AT1 receptor was chemically blocked the blood pressure would go down.
It looked pretty neat: Angiotensin acts on an AT1 receptor on an artery and the artery constricts and the blood pressure goes up. Give an AT1 blocker and the pressure comes down. Sadly, it’s not all that precise. The body is full of angiotensin receptors and they induce so many other reactions that it looks as if we have got into something as complicated as that Cytochrome P450 enzyme system we were all discussing earlier this year. In fact, some people may say that vasoconstriction is just one of the multitudinous activities of the stimulated AT1 receptor!!
How are we going to explain all this?
Very briefly. Angiotensin does cause vasoconstriction but not in a uniform manner all over the body. Some vessels constrict more than others. Vasoconstriction is strongest in the kidneys but is much less active in the brain and even weaker in the vessels of the lung and skeletal muscle. What angiotensin does, however, is to bring another system into play and that is the sympathetic nervous system. Sympathetic fibers go to almost every blood vessel in the body and stimulate vascular constriction (hence a rise in blood pressure) by the action of norepinephrine. Angiotensin increases this action, causing higher and higher blood pressure levels. Angiotensin also acts on the central nervous system where sympathetic fibers accompany the spinal nerves. Some even consider it a neurotransmitter. It even acts on the adrenal medulla liberating pressor catecholamines. (These are not to be confused with aldosterone which will be considered later.) However, Lyn thinks we should stop here as sufficient unto the day is the evil thereof.
With so much pressor activity available in the body, one would wonder why patients with Bartter’s or Gitelman’s exhibit such low blood pressure. True, blockers of the AT1 receptor lower the blood pressure of a person with hypertension and cut down the activity of the renin-angiotensin-aldosterone system in Bartter’s (a treatment to be condemned) but something just doesn’t seem quite right. In a salt deficient animal, lots of angiotensin is produced without deleterious effects on the blood vessels. Angiotensin can damage arteries. What is protecting them in salt deficiency and (although possibly a lesser extent) in Bartter’s? All opinions are gladly accepted.
We will have to consider
the effects of angiotensin on the kidneys and then the adrenals on the
next web pages.