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P A R T 8
Drugs acting on the cardiovascular system
Low blood pressure or poor oxygenation of a
nephron causes the release of renin from the juxta
glomerular cells, a group of cells that monitor blood
pressure and flow into the glomerulus. Renin is released
into the bloodstream and arrives in the liver to convert
the compound angiotensinogen (produced in the liver) to
angiotensin I. Angiotensin I travels in the bloodstream
to the lungs, where the metabolic cells of the alveoli use
angiotensin-converting enzyme (ACE) to convert angio
tensin I to angiotensin II. Angiotensin II reacts with
specific angiotensin II receptor sites on blood vessels
to cause intense vasoconstriction. This effect raises
the total peripheral resistance and the blood pressure,
restoring blood flow to the kidneys and decreasing the
release of renin.
Angiotensin II, probably after conversion to angio-
tensin III, also stimulates the adrenal cortex to release
aldosterone. Aldosterone acts on the nephrons to cause
the retention of sodium and water. This effect increases
blood volume, which should also contribute to increas-
ing blood pressure. The sodium-rich blood stimulates the
osmoreceptors in the hypothalamus to cause the release
of antidiuretic hormone (ADH), which in turn causes
retention of water in the nephrons, further increasing the
blood volume. This increase in blood volume increases
the blood pressure, which should increase blood flow to
the kidneys. This should lead to a decrease in the release
of renin, thus causing the compensatory mechanisms to
stop (Figure 43.2).
Hypertension
When a person’s blood pressure is above normal limits
for a sustained period, a diagnosis of hypertension is
made (Table 43.1). In New Zealand, heart disease that
includes hypertension accounted for 30% of all deaths
in the 2006 census. Ma– ori people were the main ethnic
group highly represented for cardiovascular death. In
Australia, the Australian Bureau of Statistics (2014)
reported in 2012–13 that 20% of the Indigenous popu-
lation over the age of 55 years had hypertension.
Ninety percent of the people with hypertension have
what is called
essential hypertension
, or hypertension
with no known cause. People with essential hyperten-
sion usually have elevated total peripheral resistance.
Their organs are being perfused effectively, and they
usually display no symptoms. A few people develop
secondary hypertension, or high blood pressure result-
ing from a known cause. For instance, a tumour in the
adrenal medulla called a phaeochromocytoma can cause
hypertension related to the release of large amounts of
noradrenaline from tumour cells, which resolves after
the tumour is removed.
The underlying danger of hypertension of any type is
the prolonged force on the vessels of the vascular system.
The muscles in the arterial system eventually thicken,
leading to a loss of responsiveness in the system. The left
ventricle thickens because the muscle must constantly
work hard to expel blood at a greater force. The thick-
ening of the heart muscle and the increased pressure that
1
4
5
6
Decreased perfusion
pressure in the afferent
arteriole stimulates
secretion of renin by
the juxtaglomerular cells.
2
Liver produces
angiotensinogen.
3
Activation of angiotensin I
to angiotensin II occurs in
the pulmonary capillary bed
by a converting enzyme.
Angiotensin II:
a powerful
vasoconstrictor
Angiotensin II becomes
angiotensin III which causes
the release of aldosterone
from the adrenal cortex.
Aldosterone causes increased
sodium and water reabsorption
by the tubules of the kidney.
Result is increased blood volume.
Arteriole
Efferent arteriole
Glomerulus
Afferent arteriole
Juxtaglomerular
cells
Angiotensin II
receptors
Renin reacts with
angiotensinogen to form
angiotensin I
Angiotensin I
Angiotensin II
ADH release
and water retention
to blood volume.
Sodium
retention
FIGURE 43.2
The renin–angiotensin–aldosterone system.
