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Having made a general study of the kidney, including some of its transporting mechanisms; and after looking at some JG cells, we are going to take a brief view of the Renin-Angiotensin-Aldosterone-System. This system has been mentioned already so it is now time to find out more about its mysterious chain of reactions.

This time we are not starting with the kidney but the liver! We all know that our blood contains serum proteins but do we know where these serum proteins come from? Well, almost all of them are manufactured by the liver.

Today, we are going to consider Angiotensinogen, one of the most important serum proteins . Angiotensinogen may be roughly translated as the “source of Angiotensin”.

Angiotensinogen is an alpha2 globulin. It is also classed as a globular protein and like all proteins it is composed of amino acids. As nobody seems to have made a diagram of it, here is one suggested by this author:

Note that this drawing represents one very big molecule. The “stem” is the future Angiotensin I that renin is going to detach. Of course, this is a rather crude way to represent a protein and besides, the “stem” could be hidden where we wouldn’t be able to see it. Nevertheless, the reaction goes on as described below.

Once it enters the circulation Angiotensinogen is attacked by that fearsome creature which is none other than RENIN. Renin, itself, does not cause vasoconstriction but is an enzyme that cleaves the Angiotensinogen molecule, removing the “stem” which becomes Angiotensin I. Angiotensin I has little activity and causes only minor vasoconstriction. Its molecule must be further modified to become that very active form, Angiotensin II.

Once we get up to Angiotensin II, it will be plain sailing but first we have to stop and think about how an inactive substance becomes such an active one. As Angiotensin I is converted to Angiotensin II it must have a converting enzyme. You have all heard about it. It is none other than ACE – Angiotensin Converting Enzyme!

This “conversion” occurs in a place you might never expect. It takes place in the lungs! Angiotensin converting enzyme is stuck to the endothelium of the little blood vessels of the lung. There it reaches out and snips off the last two units of each little molecule as it passes, thus converting it to Angiotensin II.

We have all heard of ACE inhibitors and now we can see how they act. They prevent the conversion of Angiotensin I to Angiotensin II. This is one method of cutting down the activity of the renin-angiotensin-aldosterone system. But we mustn’t get ahead of ourselves and talk about blocking agents now.

Next week we will look at vasoconstriction due to Angiotensin II and the effect of Angiotensin II on the adrenals.

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