section 32.2
Adrenal Medulla
765
accessible to both circulating (E) and neurotransmitted
(NE) catecholamines. In fact, thedistribution of the sub-
types appears to be appropriate for the ligand that is preva-
lent in a given region. For example, the /12-adrenergic
receptors (E > NE) in bronchiolar smooth muscles are
located in regions of the respiratory system that are poorly
supplied by sympathetic nerve fibers but are accessible to
agents that arrive by way of the blood supply. These recep-
tors are most likely to respond to circulating E than to neu-
ral NE, and are responsive to inhaled synthetic adrenergic
agonists (e.g., albuterol, salmeterol) that diffuse through
the mucosal surface. On the other hand, the
p {
-adrenergic
receptors in the juxtaglomerular apparatus (JGA) of the
kidney, the site of renin release that is richly supplied by
sympathetic nerve fibers but is also well vascularized, tend
to respond preferentially to neural NE rather than to plasma
E, despite the fact that this subtype is known to have equal
affinity for both catecholamines (Table 32-3). This sug-
gests that the
p
, receptors of the JGA are localized in the
synaptic clefts as postjunctional binding sites and are not
accessible to plasma-derived E.
To facilitate the discussion on the effects of cate-
cholamines (below), Table 32-3 includes a list of the
“physiological ligand” (i.e., neural NE or plasma E) for the
adrenergic receptor subtype in some of the tissues, based
on their efferent sympathetic nerve supply. The different
tissue distribution of adrenergic receptor subtypes indi-
cates the genetic influence on the kinds of receptors; how-
ever, the density of the receptor subtypes also exhibits tis-
sue variation. For example, although white adipose tissue
contains both
p ]
and
p 3
receptors, the latter is in greater
quantity in visceral adipose tissue.
The density of adrenergic receptors is strongly in-
fluenced by hormones. The adrenergic catecholamines
exert an important regulation on their own receptors,
causing downregulation when the concentrations are
raised. All subtypes of adrenergic receptors except the
p 3
subtype is subject to downregulation. Thyroid hormone
increases the density of /3-adrenergic receptors in some
tissues (heart, fat, skeletal muscle), but decreases it in
the liver. Glucocorticoids (GC) increase the density
of
P
2'-adrenergic receptors in vascular and bronchiolar
smooth muscle, and has been shown to be effective in re-
versing agonist-induced desensitization of /32-adrenergic
receptors in asthmatic patients.
Biological Effects of Epinephrine and
Norepinephrine (Table 32-3)
Although NE is present at higher concentrations in plasma
than E (Table 32-1), plasma NE is physiologically inef-
fective under most conditions. Plasma NE levels above
100 ng/dL are required for a systemic response, and such
concentrations usually are produced only during very
stressful situations (e.g., strenuous exercise or myocardial
infarct). In contrast, E is capable of activating adrener-
gic receptors at threshold concentrations of 10-15 ng/dL,
levels that are attained with relatively mild stimuli (e.g.,
cigarette smoking or hypoglycemia). E exerts important
cardiovascular, pulmonary, renal, metabolic, endocrine,
and thermogenic effects, most of which are supported or
complemented by neural effects of NE that are exerted at
the same time.
Cardiovascular, Pulmonary, and Renal Effects
E increases cardiac output by increasing both the strength
and the rate of ventricular contractions
iPP).
This effect
is augmented by the constrictive effect of E
(a2)
and NE
(a2)
on the great veins, which increases venous return to
the heart and leads to increased ventricular preload and in-
creased stroke volume. The increased cardiac output is se-
lectively directed to certain organs by the combined effects
of circulating E and neurotransmitted NE. Thus, blood
flow to the skin (subcutaneous) is reduced by the combined
vasoconstrictive effects of E
(a2)
and NE
while flow
to the gastrointestinal tract, spleen, pancreas and kidney
are reduced by sympathetic (NE) stimulated vasoconstric-
tion (oq). At the same time, E redirects the flow of blood
through skeletal and cardiac muscles by promoting dilata-
tion of the arterioles of the skeletal muscle
(P2)
and the
coronary arteries of the heart
(P2).
Because the arteries in
the brain, lungs, and liver are not directly affected by the
adrenergic catecholamines, these tissues passively receive
an increase in blood flow as a result of the augmented
cardiac output and increased blood pressure secondary to
increased peripheral resistance.
Pulmonary Respiratory System
E promotes air flow through the bronchioles by caus-
ing relaxation of their smooth muscle (bronchodilatation)
(
P
2), and thus allows for increased alveolar ventilation.
The increased blood flow through the lungs (see above)
and the increased alveolar ventilation ensure maximal oxy-
genation of blood.
Renal Urinary System
Autonomic discharge results in stimulation of ADH re-
lease due to a neurotransmitted NE effect
(a
i) on the mag-
nocellular neurons in the hypothalamic paraventricular nu-
clei. This promotes increased retention of water, which, in
turn, promotes the effective blood volume. In addition, au-
tonomic discharge causes the release of neurotransmitter
