Chapter 18
The Cardiovascular System: The Heart
683
18
thyroxine, and glucagon; the drug digitalis; and high levels of
extracellular Ca
2
1
are all positive inotropic agents.
Negative
inotropic agents,
which impair or decrease contractility, include
acidosis (excess H
1
), rising extracellular K
1
levels, and drugs
called calcium channel blockers.
Afterload: Back Pressure Exerted by Arterial Blood
Afer-
load
is the pressure that the ventricles must overcome to eject
blood. It is essentially the back pressure that arterial blood ex-
erts on the aortic and pulmonary valves—about 80 mm Hg in
the aorta and 10 mm Hg in the pulmonary trunk.
In healthy individuals, aFerload is not a major determinant
of stroke volume because it is relatively constant. However, in
people with hypertension (high blood pressure), aFerload is
important indeed because it reduces the ability of the ventricles
to eject blood. Consequently, more blood remains in the heart
aFer systole, increasing ESV and reducing stroke volume.
Regulation of Heart Rate
Given a healthy cardiovascular system, SV tends to be relatively
constant. However, when blood volume drops sharply or the
heart is seriously weakened, SV declines and CO is maintained
by increasing HR and contractility. Temporary stressors can
begins to pump more blood than the other, the increased venous
return to the opposite ventricle forces that ventricle—through
increased cardiac muscle stretch—to pump out an equal volume,
preventing backup or accumulation of blood in the circulation.
Contractility
EDV is the major
intrinsic factor
influencing
SV, but
extrinsic factors
that increase heart muscle contractility
can also enhance SV.
Contractility
is defined as the contractile
strength achieved at a given muscle length. Note in ±igure 18.22
that contractility is
independent
of muscle stretch and EDV. Con-
tractility rises when more Ca
2
1
enters the cytoplasm from the ex-
tracellular fluid and the SR. Enhanced contractility means more
blood is ejected from the heart (greater SV), hence a lower ESV.
Increased sympathetic stimulation increases contractility. As
noted on p. 676, sympathetic fibers serve not only the intrinsic
conduction system but the entire heart. One effect of norepine-
phrine or epinephrine binding is to initiate a cyclic AMP second-
messenger system that increases Ca
2
1
entry, which in turn pro-
motes more cross bridge binding and enhances ventricular con-
tractility
(Figure 18.23)
.
A battery of other chemicals also influence contractility.
Substances that increase contractility are called
positive ino-
tropic agents
(
ino
5
muscle, fiber). ²e hormones epinephrine,
Norepinephrine
Adenylate cyclase
ATP
cAMP
GTP
Ca
2+
uptake pump
Ca
2+
channel
β
1
-Adrenergic
receptor
G protein (G
s
)
Ca
2+
Sarcoplasmic
reticulum (SR)
Active protein
kinase
Extracellular fluid
Cytoplasm
Phosphorylates SR Ca
2+
pumps, speeding
Ca
2+
removal and relaxation, making more
Ca
2+
available for release on the next beat
Phosphorylates SR Ca
2+
channels, increasing
intracellular Ca
2+
release
Phosphorylates plasma
membrane Ca
2+
channels, increasing
extracellular Ca
2+
entry
Inactive protein
kinase
Ca
2+
Ca
2+
Troponin
Enhanced
actin-myosin
interaction
Cardiac muscle
force and velocity
ATP is converted
to cAMP
a
b
c
binds
to
SR Ca
2+
channel
GTP
GDP
Figure 18.23
Norepinephrine increases heart contractility via a cyclic AMP second-
messenger system.
Cyclic AMP activates protein kinases that phosphorylate three different
proteins, as shown in
a
,
b
, and
c
.
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