136
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
Circulating Catecholamines
Circulating
catecholamines
originate
from
two sources. The adrenal medulla releases cat-
echolamines (80% epinephrine, 20% norepi-
nephrine) when preganglionic sympathetic
nerves innervating this tissue are activated.
This occurs during times of stress (e.g., exer-
cise, heart failure, blood loss, emotional stress,
excitement,
or
pain).
Sympathetic nerves
innervating blood vessels are another source
of
circulating
catecholamines,
principally
norepinephrine. Normally, most of the nor-
epinephrine released by sympathetic nerves is
taken back up by the nerves and metabolized
(some is taken up by extraneuronal tissues).
A small amount of released norepinephrine,
however, diffuses into the blood and circu-
lates throughout the body. At times of high
levels of sympathetic nerve activation, the
amount of norepinephrine spilling over into
the blood can increase dramatically.
Circulating epinephrine has several direct car-
diovascular actions that depend upon the relative
distribution of adrenergic receptors in different
organs and the relative affinities of the different
receptors for epinephrine. Epinephrine binds
to ß1-, ß2-, a 1-, and ^-adrenoceptors; however,
the affinity of epinephrine for P-adrenoceptors
is much greater than for a-adrenoceptors. The
relative receptor affinities explain why, at low
plasma concentrations, epinephrine binds pref-
erentially to P-adrenoceptors. Therefore, at low
to moderate circulating levels of epinephrine,
heart rate, inotropy, and dromotropy are stim-
ulated (primarily P1-adrenoceptor mediated).
Epinephrine at low concentrations binds to
P2-adrenoceptors located on small arteries and
arterioles (particularly in skeletal muscle) and
causes vasodilation.
If a low dose of epinephrine is injected
intravenously while systemic hemodynamics
are monitored, heart rate (and cardiac out-
put) will increase, systemic vascular resist-
ance will fall, but mean arterial pressure will
change very little (Fig. 6.10). At high plasma
concentrations, the cardiovascular actions of
epinephrine are different because epineph-
rine binds to a-adrenoceptors as well as to
P-adrenoceptors.
Increasing
concentrations
of epinephrine result in further cardiac stimu-
lation along with a-adrenoceptor-mediated
activation of vascular smooth muscle lead-
ing to vasoconstriction. This increases arte-
rial blood pressure (pressor response) owing
Arterial
Pressure
(mmHg)
Heart
Rate
(beats/min)
180
Norepinephrine
140
100
60
Time (min)
Time (min)
■ FIGURE 6.10 Effects of intravenous adm inistration of epinephrine and norepinephrine on arterial pres-
sure and heart rate. A low dose of epinephrine (le ft panel) increases heart rate and arterial pulse pressure
(it increases systolic and decreases diastolic pressure) w ith little change in mean arterial pressure. These
changes occur because low concentrations of epinephrine preferentially bind to cardiac ^-adrenoceptors
(produces cardiac stim ulation) and vascular ß2-adrenoceptors (produces systemic vasodilation). Mean
pressure does not change very much because the increase in cardiac output is offset by the decrease in
systemic vascular resistance. Norepinephrine (rig h t panel) increases mean arterial pressure and arterial
pulse pressure; heart rate transiently increases (^-adrenoceptor stim ulation) and then decreases owing to
baroreceptor reflex activation of vagal efferents to the heart. Mean arterial pressure rises because norepi-
nephrine binds to vascular a1-adrenoceptors, which increases systemic vascular resistance.
previous page 149 Cardiovascular Physiology Concepts  2nd Edition read online next page 151 Cardiovascular Physiology Concepts  2nd Edition read online Home Toggle text on/off