to both an increase in cardiac output and
an increase in systemic vascular resistance.
However, even at very high circulating con-
centrations of epinephrine, the systemic vas-
cular resistance does not increase very much
above normal, or may still be reduced, because
the vasoconstrictor actions epinephrine act-
ing through the a-adrenoceptors is attenu-
ated hy the epinephrine that is still bound to
the P2-adrenoceptors. If the P2-adrenoceptors
are blocked pharmacologically,
then high
concentrations of epinephrine produce very
large increases in systemic vascular resistance
because of the removal of the P2-adrenoceptor
vasodilator influence.
heart and systemic vasculature by binding to
P2-, P2-, (Xj-, and a 2-adrenoceptors; however,
the affinity of norepinephrine for P2- and
a 2-adrenoceptors is relatively weak. Therefore,
the predominant affects of norepinephrine are
mediated through P2- and cq-adrenoceptors.
If norepinephrine is injected intravenously,
it causes an increase in mean arterial blood
pulse pressure (owing to increased stroke
volume) and a paradoxical decrease in heart
rate after an initial transient increase in heart
rate (Fig. 6.10). The transient increase in
heart rate is due to norepinephrine binding
to Pj-adrenoceptors in the SA node, whereas
the secondary bradycardia is due to a baro-
receptor reflex (vagal mediated), which is in
response to the increase in arterial pressure.
High levels of circulating catecholamines,
caused by a catecholamine-secreting adrenal
tumor (pheochromocytoma), causes tachycar-
dia, arrhythmias, and severe hypertension (sys-
tolic arterial pressures can exceed 200 mm Hg).
Other actions
of circulating catechola-
mines include (1) stimulation of renin release
with subsequent elevation of angiotensin II
(All) and aldosterone, and (2) cardiac and
vascular smooth muscle hypertrophy and
remodeling. These actions of catecholamines,
in addition to the hemodynamic and cardiac
actions already described, make them a fre-
quent therapeutic target for the treatment of
hypertension, heart failure, coronary artery
disease, and arrhythmias. This has led to
the development and use of many different
types of a- and P-adrenoceptor antagonists to
modulate the effects of circulating catechola-
mines as well as the norepinephrine released
by sympathetic nerves.
How would the changes in arterial
pressure and heart rate shown
in Figure 6.10 be different if
^-adrenoceptors were blocked before the
administration of low-dose epinephrine?
How would the norepinephrine-induced
changes in arterial pressure and heart rate
shown in Figure 6.10 be different in the
presence of bilateral cervical vagotomy?
The renin-angiotensin-aldosterone system plays
an important role in regulating blood volume,
cardiac and vascular function, and arterial blood
pressure. Although the pathways for renin and
angiotensin formation have been found in a
number of tissues, the most important site
for renin formation and subsequent forma-
tion of circulating angiotensin is the kidney.
Sympathetic stimulation of the kidneys (via
P^adrenoceptors), renal artery hypotension,
and decreased sodium delivery to the distal
tubules (usually caused by reduced glomeru-
lar filtration rate secondary to reduced renal
perfusion) stimulate the release of renin into
the circulation. The renin is formed within,
and released from, juxtaglomerular
associated with afferent and efferent arterioles
of renal glomeruli (see Chapter 7 for details),
which are adjacent to the macula densa cells
of distal tubule segments that sense sodium
chloride concentrations in the distal tubule.
Together, these components are referred to as
the juxtaglomerular apparatus.
Renin is an enzyme that acts upon angio-
thesized and released by the liver, which
previous page 150 Cardiovascular Physiology Concepts  2nd Edition read online next page 152 Cardiovascular Physiology Concepts  2nd Edition read online Home Toggle text on/off