Now, here’s some very important information,
physiologic information that relates to the
drugs that we’re going to talk about next.
It turns out that the kidney is really the
master conductor of blood pressure in the
body. So, just like the conductor of the orchestra,
the kidney conducts the blood pressure regulation
in the body. It’s interacting constantly
with the central nervous system, with the
sympathetic nervous system. But, the kidney
has all kinds of built-in measures of blood
pressure and releases hormones when the blood
pressure is too low and cuts back on certain
hormones, when the blood pressure is too high
and these hormones hold on to salt and water
and help to raise the blood pressure.
So, these little receptors are called baroreceptors,
it means pressure… pressure receptors. It’s
like a pressure gauge in the kidney that tells
the kidney, “Hey you need to either increase
some hormones that push blood pressure up
or you need to decrease some hormones that
push blood pressure down.”
And what these hormones do, that are released
from the kidney, the hormone is called renin.
Renin relates to the Latin word for kidney.
Renin… renin means kidney. So, these hormones
actually increase the blood pressure - A.
by constricting the blood… little blood
vessels, but they also result in salt and
So, you see, you increase the volume of the
cardiovascular system, of the circulating
blood. At the same time, you clamp down a
little bit on the periphery and both of those
things increase the cardiac output by increasing
the volume and increase the peripheral resistance
and they push the blood pressure up.
As I’ve mentioned a number of times in this
lecture series, this system is particularly
geared for defending against dehydration in
a very dry environment and to protect the
body at times of blood loss, for example,
with hemorrhage. The system is called the
renin-angiotensin-aldosterone system. I’ll
show you a slide of it in a moment. But, basically,
it is involved in holding on to salt and water.
It signals the whole kidney system - don’t
let too much salt and water go out and secondly,
it increases the peripheral vascular resistance
to increase the blood pressure. There’s
also hormones released from the central nervous
system that hold on to water, so called anti-diuretic
hormone. So, there’s a whole interactive
system here that’s focused on maintaining
blood volume and maintaining blood pressure.
Now, this diagram actually shows you all of
the biochemical components in the renin-angiotensin
system. To just say it very simply, the kidney
sees a lowering of blood pressure. It releases
rennin. There is a whole series of chemical
reactions from renin to angiotensinogen, to
angiotensin I, Angiotensin II. And angiotensin
I and II constrict the peripheral blood vessels
and they signal the adrenal gland to reduce…
to redu-… to release aldosterone and aldosterone
holds on to salt and water. And also, it signals
the central nervous system to release anti-diuretic
hormone, so you hold on to water. You can
see all of this interactive system is geared
at maintaining the blood volume and maintaining
the blood pressure.
Those of you who are going to be going on
to study, some more in depth the physiology,
this renin-angiotensin system is an important
system studied in renal physiology and it
is essential for blood pressure control. And
so, I’m already hinting at this. No surprise.
What we try and do in patients with high blood
pressure is block some of the aspects of this
system and you will see that as we go along.
And you saw on the diagram there, there were
two drugs - ACE inhibitors, angiotensin converting
enzyme inhibitors and angiotensin receptor
blockers that actually block the effect of
the renin-angiotensin system and thereby,
lower blood pressure. We’re going to talk
about those in more detail in just a couple
of minutes. In any case, this system is critical
for regulating blood volume and blood pressure.
It is, as I said before, the conductor of
the orchestra for maintaining blood pressure
and blood volume.
This slide demonstrates the most commonly
used angiotensin converting enzyme inhibitors,
ACE inhibitors and the most commonly used
angiotensin… angiotensin receptor blockers.
Again, most doctors won’t use each of these
drugs. They will pick one in each category
and use them.
Most popular in the United States is lisinopril.
It’s a once a day drug, it’s generic,
it’s inexpensive, very effective with minimal
side effects. The most important angiotensin
receptor blocker is losartan, that’s the
most popular one in the US, also generic,
inexpensive and a very low side effect profile.
These drugs, again, to remind you, are first
line treatment for controlling hypertension.
The ACE inhibitors, in an occasional patient,
will set off an allergic reaction with swelling
of the face and tongue and obviously, we don’t
want to use a drug that causes swelling of
the tongue in those patients. But, it’s
a fairly rare number that does that. And both
drugs can excessively lower blood pressure,
make people light headed and dizzy, particularly
at higher doses. So, you have to be very careful
about regulating the dose. And both of them
have the propensity to damage the kidney,
if the kidney already has pre-existing kidney
disease. So, if your kidneys are healthy,
there’s no problem. But, if you have some
kidney disease, you have to be careful about
using these drugs and often we use very low
doses or we don’t use them in people who
already have had kidney injury, for example,
Another important first line drug in the control
of hypertension are aldosterone blockers.
Remember, from the renin-angiotensin system,
one of the things that happens is the adrenal
gland is signaled to release aldosterone.
Aldosterone goes to the kidney and causes
it to hold on to salt and water, of course,
raising the blood volume and raising the blood
pressure. If you give blockers of aldosterone,
you decrease the tendency to hold on to salt
and water and you decrease the blood pressure.
These drugs are very effective, they're also
generic and also inexpensive with minimal
side effects. These drugs are very popular.
They're also used in heart failure, again,
because heart failure patients have retained
too much salt and water. So, they're good
in hypertension and they’re good in heart
By the way, each of these drugs that’s good
for hypertension are also good for heart failure
because one of the things we want to do is
you remember from the heart failure lecture,
is we want to decrease the work of the heart.
You lower the blood pressure, the heart has
to work less and maybe it can heal itself
when it’s been injured.
Here we see a little diagram of the kinds
of things that an aldosterone inhibitor does.
It decreases the likelihood of holding on
to sodium. As you see on the left hand part
of the slide, it decreases the likelihood
of holding on to water. It also has a very
beneficial effect, it holds on to potassium.
So, the tendency for hypokalemia, remember
I talked about, you don’t want hypokalemia
because it can cause cramps and heart arrhythmias?
Well, aldosterone blockers actually increase
potassium and they work against hypokalemia.
Also, they can work against scarring in the
heart, as you see on the right hand side.
Collagen is one of the major components of
scar. And so, they can actually improve the
flexibility of the heart by a small amount.
So, they have a number of benefits in patients
with high blood pressure.
Well, let’s talk about Beta Blockers. We
talked about these drugs both for heart failure