Activating angiotensin 2

So we've talked a lot about the kidney, but I want to point out that the kidney is not the only organ that's involved in controlling your blood pressure. And in fact, the liver plays a really, really important role in helping you create the right enzymes and proteins to control your blood pressure. So I'm going to sketch out, real quick, some liver cells here. And these liver cells are busy making a lot of different proteins. One of them is actually called angiotensinogen. So angiotensinogen gets made by these little liver cells. And they dump it out into the blood vessel, just like that. And if you were to draw angiotensinogen, it's actually a pretty large molecule. And it has lots and lots of amino acids. And amino acids are these tiny little circles that I'm drawing. And I'm connecting them with little bonds. So you can imagine amino acids being like pearls on a necklace. And in total, angiotensinogen has about 450 plus amino acids. So it's a pretty long chain, 452, actually, amino acids. So it's a pretty long chain. I'm not going to draw all of it, but you get the idea that it's some crazy long chain like that, and little amino acids strung together all the way through. So this huge, huge protein gets put into the blood vessels by the liver cells. And that starts floating around. And if you were to actually zoom in on the little protein, if you could give it a face, it would maybe look something like this, because, even though it's floating around the body and it's going to different parts of the body, it's basically asleep. It's not really active. And I just want you keep that tucked in the back of your mind, that even though it's there, it's not truly active. It's not really doing a whole lot. So at the same time, you know you also have the kidney. And the kidney is not idle. The kidney is busy making a hormone of its own. So you know that there is the afferent arteriole. Afferent arteriole is the blood vessel that's headed into the glomerulus. So it's actually headed on its way into the part of the kidney where all of the urine is initially made. So the afferent arteriole, blood is going that way. And lining this afferent arteriole, you remember, there are little cells all the way through like this. And these are called juxtaglomerular cells. I'm actually doing a simplified version of it, because this is the part that I really want to focus in on right now. And these juxtaglomerular cells have in them little granules. And they're sometimes even called granular cells, you might recall. And these granular cells sense-- either themselves or one of their neighbors help them sense-- when the blood pressure is low. And these granules get dumped into the bloodstream and actually eventually become-- or at the very microscopic level, if you were to look, you could actually see that these are little, little proteins called renin. And these are proteins that act at a distant site. And so any time you have proteins that act on cells that are far, far away, we call those hormones. And so these peptide or protein hormones are basically going to work on cells far away. And so if the renin is floating around in the blood, and the angiotensinogen is floating around in the blood, they might meet up, right? So they might meet up in your blood vessel in your arm, or they might meet up in your blood vessel in your leg, or in your abdomen. So they might meet up wherever, right? Somewhere in your body, these two protein hormones are going to meet up. And when they do, a really interesting thing happens. So just keep in mind that angiotensinogen is kind of asleep, and renin meets up with it. So what happens when they meet up? It's pretty much a meeting of two messengers, right? And these two messengers are going to have an interaction. And this is what's going to happen. So you have your angiotensinogen. It looks like this, right? Five, six, seven, eight, nine, ten. And I'm going to, as I did before, just kind of draw this long tail. And you know this is about 442 amino acids long, because that's what's left over. And the renin comes in right here. And now you can see why I purposefully kind of drew renin as a little Pac-man, because what it does is it cuts. It will chop off a huge chunk of that angiotensinogen molecule. And so what you're left with, after renin has gotten through with it, you're left with 10 amino acids, something like that. So you have 10 amino acids there Then you have, of course, you have that long chain. That is going to be tossed aside. And it will not come into use any further in this story. And so you have that long chain of amino acids. But then you have that chain of 10 amino acids. And this chain of 10 is called angiotensin 1. And you remember, we kind of drew out angiotensinogen as being asleep. And now angiotensin 1 is awake. So this renin, the key thing that it did is kind of activate angiotensin into something that is awake and able to do something of its own. So angiotensin 1, now this is still a hormone. It's still a messenger. And it continues to float around. So it's still making its way around the body. And at some point, it's going to get into the tiny little capillaries. And I'm drawing them very teeny, tiny on purpose here. So tiny little capillaries. And you know capillaries have little endothelial cells. In fact, these capillaries are usually only one cell layer thick, right? So it's really just the endothelium that is sitting there. And this endothelium is really, really interesting, because it has an enzyme that sits on its surface. So if you looked at the endothelial cells very carefully under a microscope, you might notice something like this. It's got little enzymes. And I'm trying to draw a little diamonds here on the surface. And that's because these enzymes are called angiotensin converting enzyme. So that's the name of these enzymes. And actually, you can imagine people don't like to say the whole thing all the time. They try to shorten it to ACE. So if someone says, oh yeah, I've got some endothelium here with ACE in it, you know they're talking about the fact that there's a little enzyme sitting on the edge of the cell, like that. And these little enzymes are just waiting for angiotensin 1 to pop through. So this is my angiotensin 1. I'm drawing it kind of tiny, so that I can actually show it to you. And when it touches that little angiotensin converting enzyme, two of the amino acids pop off. Two of them are actually cut off. And so you can see that I went from 10 amino acids to eight amino acids. And it will happen everywhere. So let's say you've got three, four, five, six, seven, eight. And then you'll get two popped off right there. So basically, this angiotensin converting enzyme that sits in the capillaries is going to chop off two of the last amino acids and leave you then with just eight amino acids. So in the blood vessel, then you have just eight amino acids. Draw that like that. And this eight-amino acid enzyme is called angiotensin 2. And again, if you were to draw it kind of as a human face, it would be awake, as before. But this time, it would be very happy. And the reason it's so happy is that it's very, very active. And so this is kind of an example of less is more, right? Because you started with 452 amino acids, and finally cut it down to 10, and then to eight. And now that it's eight amino acids, it's super active. It's very, very primed and ready to carry out its function. And you'll see what that is. But I wanted to just show you very quickly how renin gets the process started by chopping off a huge chunk, and how the angiotensin converting enzyme in the little capillary beds also do a trick. And actually, I should mention very briefly, for many, many years, for a long time, it was always thought that these angiotensin converting enzymes were just found in the lungs. In fact, many books still say that. But actually, more and more, we're seeing that it's found definitely in the lungs. I mean, a lot of the angiotensin converting enzyme is there, but there are many other parts of the body, including the kidney, where you can find that enzyme as well, a lot of other capillary beds. So let's stop there. And we'll pick up with angiotensin 2 in the next video.