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P A R T 8
Drugs acting on the cardiovascular system
heart failure and cases of hypotension. The supply is
most frequently altered, however, when the coronary
vessels become narrowed and unresponsive to stimuli to
dilate and deliver more blood. This happens in athero
sclerosis or coronary artery disease. The end result of
this narrowing can be total blockage of a coronary
artery, leading to hypoxia and eventual death of the cells
that depend on that vessel for oxygen. This is called a
myocardial infarction (MI), and it is one of the leading
causes of death in Australia and New Zealand.
Systemic arterial pressure
The contraction of the left ventricle, which sends blood
surging out into the aorta, creates a pressure that con
tinues to force blood into all of the branches of the
aorta. This pressure against arterial walls is greatest
during systole (cardiac contraction) and falls to its lowest
level during diastole. Measurement of both the systolic
and the diastolic pressure indicates both the pumping
pressure of the ventricle and the generalised pressure in
the system, or the pressure the ventricle has to overcome
to pump blood out of the heart.
Hypotension
The pressure of the blood in the arteries needs to
remain relatively high to ensure that blood is delivered
to every cell in the body and to keep the blood flowing
from high-pressure to low-pressure areas. The pressure
can fall dramatically—termed hypotension—from loss
of blood volume or from failure of the heart muscle
to pump effectively. Severe hypotension can progress
to shock and even death as cells are cut off from their
oxygen supply.
Hypertension
Constant, excessive high blood pressure—called hyper
tension—can damage the fragile inner lining of blood
vessels and cause a disruption of blood flow to the
tissues. It also puts a tremendous strain on the heart
muscle, increasing myocardial oxygen consumption and
putting the heart muscle at risk. Hypertension can be
caused by neurostimulation of the blood vessels that
causes them to constrict, subsequently raising pressure,
or by increased volume in the system. In most cases, the
cause of hypertension is not known and drug therapy
to correct it is aimed at changing one or more of the
normal reflexes that control vascular resistance or the
force of cardiac muscle contraction.
Cardiac:
Hypertension
Vasomotor tone
The smooth muscles in the walls of the arteries receive
constant input from nerve fibres of the sympathetic
nervous system. These impulses work to dilate the
vessels if more blood flow is needed in an area; to
constrict vessels if increased pressure is needed in the
system; and to maintain muscle tone so that the vessel
remains patent and responsive.
The coordination of these impulses is regulated
through the medulla in an area called the cardiovascu
lar centre. If increased pressure is needed, this centre
increases sympathetic flow to the vessels. If pressure
rises too high, this is sensed by baroreceptors or pres
sure receptors and the sympathetic flow is decreased.
Chapter 43 discusses the drugs that are used to influence
the stimulation of vessels to alter blood pressure.
Renin–angiotensin–aldosterone system
Another determinant of blood pressure is the renin–
angiotensin–aldosterone system. This system is activ
ated when blood flow to the kidneys is decreased. Cells
in the kidney release an enzyme called renin. Renin
is transported to the liver, where it converts angio
tensinogen (produced in the liver) to angiotensin I.
Angiotensin I travels to the lungs, where it is converted
by angiotensin-converting enzyme (ACE) to angiotensin
II. Angiotensin II travels through the body and reacts
with angiotensin II receptor sites on blood vessels to
cause a severe vasoconstriction. This increases blood
pressure and should increase blood flow to the kidneys
to decrease the release of renin. Angiotensin II also
causes the release of aldosterone from the adrenal
cortex, which causes retention of sodium and water,
leading to the release of antidiuretic hormone (ADH)
to retain water and increase blood volume. Increasing
blood volume increases blood flow to the kidney. This
system works constantly, whenever a position change
alters flow to the kidney or blood volume or pressure
changes, to help maintain the blood pressure within a
range that ensures perfusion (delivery of blood to all of
the tissues) (Figure 42.9).
Venous pressure
Blood in the veins also exerts a pressure that may some
times rise above normal. This can happen if the heart is
not pumping effectively and is unable to pump out all
of the blood that is trying to return to it. This results
in a backup or congestion of blood waiting to enter
the heart. Pressure rises in the right atrium and then
in the veins that are trying to return blood to the heart
as they encounter resistance. The venous system begins
to back up or become congested with blood.
Heart failure
If the heart muscle fails to do its job of effectively
pumping blood through the system, blood backs up
and the system becomes congested. This is called heart
failure (HF). The rise in venous pressure that results
from this backup of blood increases the hydrostatic
