Let’s just say a few things about the humoral
mechanism. As I’ve already intimated, the
humoral mechanisms – that is the hormones
that are released that help control blood
pressure – are also intimately connected
to the central nervous system. And the kidney's
again the critical factor here.
I’ve already mentioned that when blood pressure
goes down or blood volume goes down, the kidney
has a little volume and blood-pressure measuring
system in it. And I’m going to show you
a picture of that in a moment. And that system
causes release of the hormone renin. And that
renin, as I talked about, gets into the bloodstream,
causes conversion of a chemical called angiotensinogen
to angiotensin – that’s a vasoconstrictor
– and also signals the adrenal to release
aldosterone to hold on to salt and water for
So the critical factor here is that we are
trying to regulate blood pressure at a very
even and smooth level and that, unfortunately,
some people have their blood pressure regulation
set at too high a level.
It’s important also to remember that this
whole system is part of the body’s defence
against dehydration and blood loss but, unfortunately,
in a significant part of the population it’s
set at too high a level. The blood pressure
is excessively high and that leads to damage
to the organs that we’ve talked about before.
Now this fairly complicated diagram just shows
you all of the various hormonal mechanisms
that are involved in regulating the blood
pressure. Particularly one should pay attention
to what’s on the right side there. That
is the ACE pathways: that’s the angiotensin-converting
Remember, I mentioned the kidney, when it
sees that there’s not enough blood pressure,
releases renin. Renin gets out into the circulation
and, in combination with a hormone called
angiotensin-converting enzyme, it produces
the very vasoconstrictive hormone angiotensin
So you need not only renin but you also need
the so-called ACE enzyme – that angiotensin
converting enzyme. And one of our most effective
drugs at treating hypertension is a blocker
of the angiotensin-converting enzyme. So what
that means is the renin may be released but
it doesn’t cause vasoconstriction because
angiotensin is not produced because you’ve
blocked the enzyme that’s needed for that
We can also block, at the level of these vascular
smooth muscle, we can block the effect of angiotensin with
an angiotensin-receptor blocker. It turns
out that there’s an angiotensin-receptor
blocker and there’s an angiotensin factor
that increases the activity of angiotensin.
That’s angiotensin-II receptors. We’ll
talk a little bit about that but the major
one in control of blood pressure is angiotensin
I. And I’ll show you why that is in just
I just want to say a few words about the blood-pressure
measuring system within the kidney.
Within the glomerulus – which is the little
filtering system in the kidney – there is
a structure called the macula densa which
actually monitors blood pressure in the glomerulus.
If the macula densa perceives that blood pressure
is too low, it releases renin from an area
called the juxtaglomerular cells. And these
then are released into the circulation and,
as we talked about, they get into the system,
convert angiotensinogen to angiotensin. And
angiotensin then is a powerful vasoconstrictor.
But also renin gets to the brain and signals
the sympathetic nervous system to clamp down.
So all of these things are working, as you
can see, to increase peripheral resistance
to hold blood pressure elevated.
And, as we also said, when the renin gets
to the central nervous system, it results
in the pituitary releasing antidiuretic hormone
– ADH, it’s also called vasopressin – and
that tells the kidney, “Hold on to salt
and to water.”
And as you can see here all of these mechanisms
– the thermostats if you will of the brain
– are located in the hypothalamus. That’s
the critical area of the brain for controlling
the internal environment, the homeostasis
environment of the body.
So let’s talk a little bit about angiotensin.
Remember, I said there were two types of receptors
for angiotensin: type I and type II. Type
I is the one that’s involved in high blood
pressure. And we can control that by blocking
the production of angiotensin with the angiotensin-converting
enzyme inhibitors or we can actually block
the receptor on the smooth muscle that responds
to angiotensin. And those drugs are called
angiotensin-receptor blockers. They do the
same thing basically mechanistically. They
prevent the release of renin from causing
These hormonal receptors are also activated
by sympathetic nervous activity. And they
also result in marked increase in renal sodium
reabsorption and decreased renal blood flow
when they cause vasoconstriction. So there’s
a whole series of interactive mechanisms here.
But all of that is triggered by release of
renin from the kidney when the receptors in
the glomerulus say the blood pressure is low.
The problem with chronic stimulation of the
angiotensin receptor is that it can lead to
thickening of the arterioles, vascular smooth
muscle cell growth. And what happens there
indeed is that increases the resistance
and therefore perpetuates increased peripheral
vascular resistance and hypertension.
High blood pressure, just like when
any muscle is exercised a lot, the heart muscle
gets exercised a lot when there’s high blood
pressure and that causes thickening of the
left ventricular wall – left ventricular
hypertrophy – and this causes a whole variety
of changes in the pumping ability of the heart.
Also the high blood pressure can cause damage
to the glomerulus so that kidney function
decreases. You can have thickening of the
vascular media of the smooth muscle and that
increases peripheral vascular resistance even
in slightly larger arteries, even in the arterioles.
The endothelium with its release of vasodilating
hormones can be impaired. That further increases
peripheral resistance. You can get thickening
of the intima which further increases peripheral
vascular resistance. And of course hypertension
is one of the factors that leads to increased
atherosclerosis and stroke. And, as you know,
hypertension is one of the major risk factors
It’s also been found that the increased
blood pressure in the brain eventually damages
brain cells and causes dementia – that is
decreased brain function. People become forgetful,
confused and so forth.
Now it turns out that, as so often happens
in the body, it’s like a see-saw. Every time
there’s a chemical or a hormone that works
one way there’s a chemical that works in
the opposite direction. Or a receptor that
works in the opposite direction.
The receptor that works in the opposite direction
of the angiotensin-I receptor is the angiotensin-II
receptor. And this receptor is involved in
a number of cell activities: proliferation,
or dividing of the cells; differentiation,
or development of the cells; development of
blood vessels, angiogenesis; wound healing;
tissue repair; and cell death.
But when we talk about angiotensin-II receptors,
they really have no role in blood pressure.
So they’re really a much greater interest
to the surgeons and there’s some experimental
drugs involved in trying to use these for
helping and healing and so forth.
But in fact the angiotensin-II receptor does
not play a role in the control of blood pressure.
It’s the angiotensin-I receptor. And the
drugs that we use to control high blood pressure
– one of the drugs – is a blocker of the
angiotensin-I receptor. So that the blood
vessels don’t vasoconstrict as much because
the angiotensin doesn’t cause smooth muscle
contraction when the angiotensin-receptor
blocker is in the bloodstream