Now, you have this really cool diagram in
your notes. I want you to take a look at it.
It shows you where all the players of the
RAAS. What organs they come from,
what comes from the liver, what comes
in from the juxtaglomerular cells,
what comes from the lungs,
what happens in the capillaries and
what happens -- It's really neat.
So I want you to pause the
video for a second.
Just take a look at it, orient
yourself to that picture,
and then restart the video when you're ready.
Now let's break the RAAS down
very simply. Okay,
some reason your body senses, "Wow,
we need to raise the blood pressure."
Maybe it senses a drop in the blood pressure,
maybe it senses a low sodium.
Whenever that alarm bell goes off,
the juxtaglomerular cells
in the kidneys. Now,
you may not be proud of me for saying
that, but that word scares me to death
every time I have to say it;
so I'm pretty impressed that I got it out.
But renin is excluded from these j cells
in the kidney because, why?
The body sensed a need to
raise blood pressure.
So that's why renin -- that's squirted
out through your kidneys.
Now, renin connects up with
When you're looking at your
where does angiotensinogen come from?
What liver-colored organ does
angiotensinogen come from?
When renin and the circulating
angiotensinogen meet up,
you end up with a different product:
Okay, so I went from renin
to circulating angiotensinogen.
Well, why did the renin appear?
Because my body sensed I needed
to raise my blood pressure.
So, renin connected to the
I end up with angiotensin I.
Now, when angiotensin I
meets ACE, or angiotensin-converting enzyme,
you end up with -- angiotensin II.
This is another bad mama jama.
This causes potent vasoconstriction
and volume expansion.
So, the RAAS is a system --
1 of the 5 key players
that my body uses to maintain
The renin -- Can you remember the
reason that renin appears?
Why does the body put that out? Why do
those j cells in the kidney, put out renin?
Renin connects with angiotensinogen,
then you end up with angiotensin I.
Angiotensin I hits ACE, angiotensin-converting
enzyme pretty cool name, right?
And you end up with angiotensin II.
The end result of angiotensin II,
my blood pressure is raised 2 ways, with a --
potent vasoconstriction and --
So what does that mean? That reminds me
of that little girl in Willy Wonka.
Remember when she said, "I want it now."
She was the blueberry girl and she --
that volume blew right up, so that's
why I'll use that to remind you.
So look at the breakdown on the
bottom of your screen.
Why are we going over this
over and over again?
Because that's a great study tip for you.
Repetition really helps your
brain remember things.
It likes to see things that it's familiar.
So, renin plus angiotensinogen
equals angiotensin I.
Then angiotensin I
connects with ACE and you end
up with angiotensin II.
Now there's 2 ways the
release of angiotensin II
raises your blood pressure.
Can you remember the 2 ways -- and you
don't have to do the sound effects --
but remember the 2 ways that angiotensin
II raises your blood pressure?
Okay, so we're not done with this.
We're going to keep going
over and over this concept because
this is the key to understanding
multiple high blood pressure
Just understanding how the RAAS
works will make it so much easier
for you to understand these types
of medications. So,
the 2 reasons that your blood
because of the end product
of RAAS angiotensin II,
are volume expansion and vaso constriction.
Now, you know the sound effects
that go with that, right?
Vasoconstriction and -- volume expansion.
Now, the volume expansion comes
The adrenal gland releases aldosterone.
Now, why would I say it like that? Because
most normal people don't say
1, it's pretty annoying, and 2, it's
something you didn't expect
and will help it stick in your brain better.
So, while you don't have to agree
with the way I do things,
anything you can do while you're studying
that makes something stick in your mind,
then you'll say aldosterone. I remember that.
I can be in the mall, and I'll meet
somebody who I had
10 years ago in Pharmacology and they'll say,
"Hey, Prof. Lawes, aldosterone," and I think, "Yes."
So anything that's weird or unexpected
that helps you remember
information, go with it.
You might not want to say it in public,
but it'll definitely work in your studying.
So when the adrenal gland
that means the body hangs on
to sodium. Those kidneys
will hang on to sodium, and
you know the rule.
Wherever sodium goes, water follows.
So, volume expansion comes from
the release of aldosterone.
That means the body hangs on to
sodium, and wherever sodium goes,
Now, the vasoconstriction that
comes from angiotensin II,
it is a very, very potent vasoconstrictor.
Like, 4-8 times as active as norepinephrine.
Norepinephrine is a drug that we use
usually in the critical care setting
for someone who is desperately, life-
threateningly low blood pressure.
So, this, angiotensin II, which my own body
is capable of making with the RAAS,
is 4-8 times as potent
It's really impressive. That's why I
told you it is a bad mama jama.
So, the RAAS, the end products of that,
end up with volume expansion
Now without looking at the screen,
what I want you to do is to think through
this diagram, see if you can look
in the margin of your notes
and recreate this diagram without
looking at the notes.
Okay, now, let's pretend that we have
unlimited resources and finances,
and you and I are going to solve the
problem of treating hypertension.
Now, if we look at this process,
like a flow chart --
so let's say this is how the RAAS works,
right? We've got renin,
angiotensinogen, angiotensin I,
ACE, and angiotensin II.
Okay, so what kind of drugs could I
design, based on these steps--
how could I interrupt these steps
or interfere with these steps,
and so I don't make it all the way down
to the action of angiotensin II?
Now, there is a point I want to point out.
Angiotensin II, we know it is a really
intense concept, right?
It's a really amazing what it
can do in the body,
but it doesn't really do anything
unless angiotensin II
has available angiotensin II receptors.
So before I get that -- all that
reaction that we get,
you want to make sure that
the angiotensin II
can actually make it to an
angiotensin II receptor.
Now that was a really big clue.
If we're in an escape room together, that
would have been a really big clue,
but let's walk through it.
Because what would happen if we for
say, used direct renin inhibitors?
If we could make a drug that
would inhibit renin?
Well, look at that. If I have less renin,
I'm going to end up with less angiotensin II,
and I'm going to end up with
less angiotensin I, right,
because there won't be as
much renin available
to connect with the circulating
therefore, I have less of every
other product downstream.
Okay, cool. So if I have less renin,
I'm going to end up with less
potent vasoconstriction and
volume expansion, because there's just
going to be less available.
So that would be cool if we could come
up with a drug that would do that.
Now, what if I could come up with a drug
that just made less ACE available, less
Well, I'd still have lots of renin,
angiotensinogen would be there.
I'd have angiotensin I, but --
ah, that's why I wouldn't have as much -- and --
because if I have less ACE, I have less
things available to convert
angiotensin I to angiotensin II.
Bueno, that means I will be able to
lower my patient's blood pressure.
Okay, so we've talked about
direct renin inhibitors,
and we've talked about ACE inhibitors.
So we've hit the inhibitors. Let's talk
about the blockers, okay?
So, we've got a choice of angiotensin
II receptor blockers
or aldosterone receptor
antagonist, or blockers.
Okay. So, if I could create
a drug that was an
angiotensin II receptor blocker,
that means that that is a drug --
Remember, we've got unlimited
resources and money.
That's a drug that is so uniquely
created that it will slide
right into an angiotensin II receptor.
And once that drug is on there,
it blocks off that receptor.
So let's walk back through our flow chart.
If I've given my patient an angiotensin II
receptor blocker, will I have renin?
Yes. Okay, well, then will I have
Yes. Well, then will I have angiotensin I?
Yes. But if I've given them an angiotensin
II receptor blocker, will I have ACE?
Yes. So, will I end up with angiotensin II?
Yes, you will, but here's the deal.
It'll be all dressed up and no place
to go because why?
Because you were smart enough
to give your patient an
angiotensin II receptor blocker.
Well, look at this receptor down
here. It's all filled up.
So when your body squirts out
those substances and
angiotensin II becomes available,
it can't connect to the receptor
because you wisely gave your patient
an angiotensin II receptor blocker.
So, without that angiotensin II
connecting to the receptor,
you're not going to have the potent --
vasoconstriction or volume expansion.
Now, we've got another blocker up there.
You can see that we called it an antagonist.
Remember, we use those terms interchangeably,
"antagonist" and "blocker."
So, an aldosterone receptor antagonist,
the same thing as an
aldosterone receptor blocker.
So, if I have a med that's an aldosterone
that means that that medication is
uniquely created, that it will fit
and block the aldosterone receptors.
With the receptors not being available,
because you gave the patient a medication,
the body's not going to know to
hang on to sodium, right?
So you're not going to have
that water that follows,
so your blood pressure will be lower.
So that's why understanding how the RAAS
works before we ever talked about the drugs,
really, can help you understand
their mechanism of action.
If we have less renin, we definitely
have less angiotensin II.
If we have less ACE, angiotensin-
we're definitely going to have
less angiotensin II.
If we have an ARB, an angiotensin
II receptor blocker,
we're going to have angiotensin II,
but without its ability to connect
to an angiotensin II receptor,
we're not going to have that normal
vasoconstriction or volume expansion.
If we try a patient on an aldosterone
we're not going to have the body
hanging on to more sodium
with water following for the
So understanding the RAAS is a really
simple and straightforward way
to look at 4 groups or categories
of antihypertensive medications.