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Physiology A: AUTONOMIC NERVOUS SYSTEM

Lectured by: Dr. Valerio

Autonomic Nervous System (defn)

Structures of the nervous system

12 Pairs of Cranial Nerves

Portion of the nervous system which controls the visceral functions of the body
1. Cardiac function
2. Blood pressure
3. Respiration
4. Glandular activity
1. Brain
2. Spinal Cord
3. Cranial Nerves
4.
Spinal Nerves
5. Ganglia
6. Enteric Plexus
7. Sensory Receptors
Mnemonic: Oh Oh Oh To Touch And Feel Very Green Vegetables AH
I.
Olfactory
II. Optic

III. Oculomotor
IV.
V.
VI.

Trochlear
Trigeminal (Opthalmic/Maxillary/Mandibular)
Abducens

VII. Facial
VIII. Vestibulocochlear

IX. Glossopharyngeal
X. Vagus Nerve

31 Pairs of Spinal Nerves

XI. Accessory Nerve


XII. Hypoglossal Nerve
Note: Cranial Nerves that are part of ANS III, VII, IX, X
8 Cervical Nerves (C1-C8)

12 Thoracic Nerves (T1-T12)


(Note: highlighted - part of ANS)

5 Lumbar Nerves (L1-L5)


5 Sacral Nerves (S1-S5)
5 Components of a Reflex Arc

Reflex Arc Activity

Sensory Receptors

4 Types of Nerve Fibers


Afferent (Sensory)

Efferent (Motor)

Divisions of the Peripheral Nervous System


CPalafox (1A)

Cervical Plexus
Brachial Plexus
Intercostal/Thoracic Nerves
Subcostal nerve
Lumbar Plexus
Sacral Plexus

1 Pair of Coccygeal Nerves/Roots


1. Sensory receptors
2. Afferent nerve is a sensory nerve, transmits sensory impulses from the sensory receptors to the
center
3. Center CNS (brain and spinal cord)
4. Efferent nerve - is a motor nerve, transmits motor impulses from the center to the different
effector cells
5. Effector Cells four types (Skeletal, cardiac, smooth muscle, glands)
1. Receptor potential local potential generated by sensory receptors when stimulated.
2. If threshold voltage, Local Potential  Action Potential / Sensory Impulse - Transmitted by an
afferent nerve to the center.
3. The center will analyze the sensory impulse, and then generate a motor impulse.
4. Motor impulse will be transmitted by efferent nerve to the different effector cells/organs.
5. Effector cells perform the function, as dictated by the motor impulse.
Sensory receptors are specialized structures located in almost all parts of the body, stimulated by changes
inside/outside the body.
1. Mechanoreceptors (ex. intestinal walls, stretching of walls because of retained food)
2. Thermoreceptors (ex. skin, changes in temperature)
3. Photoreceptors (ex. eyes, changes in the wavelength of light)
4. Chemoreceptors (ex. mouth, chemical composition of food)
5. Baroreceptors (ex. blood vessels, arterial wall is stretched during BP increase)
6. Nociceptors (ex. Free nerve endings for pain)
Somatic
Visceral
1. Somatic Afferent (Sensory)
2. Visceral Afferent (Sensory)
From:
To:
From:
To:
Head
CNS
Viscera (Internal organs)
CNS
Body wall
Extremeties
3. Somatic Efferent (Motor)
4. Visceral Efferent (Motor)
From:
To:
From:
To:
CNS
Striated Voluntary
CNS
Internal Organs
Muscles (Skeletal
Glands
Muscles)
Smooth and Cardiac
(Involuntary) Muscles
SOMATIC NERVOUS SYSTEM
AUTONOMIC NERVOUS SYSTEM

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

Peripheral Nervous System


1.
2.
Central Nervous System
1.
2.
Difference between Somatic and
Autonomic Nervous System

PERIPHERAL NERVOUS SYSTEM


12 pairs Cranial Nerves and its branches (originating from the brain stem)
31 pairs Spinal Nerves and its branches (originating from the segments of the spinal cord)
CENTRAL NERVOUS SYSTEM
Brain
Spinal Cord
Somatic
Autonomic

Reflexes

VOLUNTARY MOVEMENT / CONSCIOUS /


DELIBERATE RESPONSE

Function

Orients individual to the external environment;


bring about movement for locomotion
Located in the head, body wall, extremeties

Somatic senses (tactile, thermal, pain and


proprioceptive sensations) and

Special senses (vision, hearing, taste, smell


and equilibrium)

One-neuron fiber, directly forms a link


with the effector cell at the
neuromuscular junction (NMJ)

Sensory Input/ Receptors

Structure of the Efferent Nerve / Fibers

single Somatic Efferent Fiber


ONE NEURON PATHWAY:

Main Center
Effector Cell / Innervation
NTA
Inhibit or Block transmission of motor
impulses
Effect if innervation is cut

Excitation / Inhibition

Subdivisions of ANS

Enteric NS

1.
2.

3.
4.
5.
Anatomical Differences between SNS and
PSNS
Origin of Pre-ganglionic fiber
CPalafox (1A)

Visceral Efferent Fibers divided by the


peripheral ganglion (PG)
TWO NEURON PATHWAY

Preganglionic (CNS- Preganglion-PG)

Postganglionic (PG-PostganglionEffector)
Exception: Adrenal Medulla (CNS-AM) fiber
is identical to autonomic preganglionic
fibers; cells of AM are identical to
autonomic postganglionic fibers

CNS - Somatic Efferent Fiber Effector Cell )

Mainly by Cerebral cortex; lesser by basal


ganglia, cerebellum, spinal cord
Skeletal striated muscle
Acetylcholine
At 2 locations: Center and NMJ junction

INVOLUNTARY MOVEMENT / UNCONSCIOUS /


AUTOMATIC INSTANTANEOUS RESPONSES
Note: some are mostly involuntary/partly voluntary
(respiration, micturation, defecation)
Regulates functions of different internal organs; involved
in constancy of internal env. of the body (HOMEOSTASIS)
Located in internal organs
Associated with interoceptors (sensory receptors in
blood vessels, visceral organs, muscles and nervous
system) that monitor conditions in the internal
environment

Two-neuron fiber, synapse first with


peripheral/autonomic ganglion

Autonomic ganglion neuron outside the CNS;


located at the center.

No contraction if nerve is cut; complete


paralysis, atrophy
NON AUTOMATIC cell ex. Skeletal
muscle cell

Always leads to excitation of the muscles


(Contraction of the skeletal muscle)

Hypothalamus, brain stem, spinal cord


Visceral/ Smooth, cardiac muscle, or gland cells
Acetylcholine and Norepinephrine
At 3 locations: Center, Peripheral Ganglia, Neuroeffector
Junctions

Can maintain activity

Cardiac has automatic cell; ex. synoatrial node

Visceral cells also have automatic cells.

AUTOMATIC cell capable of generating its own


action potential spontaneously, independent of
stimulation.

Can lead to excitation or inhibition of the effector


cells
 Smooth Muscle: contraction or relaxation;
 Cardiac: increased or decreased rate and force
of contraction;
 Glands: Increased or decreased secretion of
glands)

1. Enteric NS
2. Sympathetic NS (SNS)
3. Parasympathetic NS (PSNS)
GIT Has its own nervous system
Neurons lie in the GIT wall (esophagus to anus):
a.
Myenteric or Auerbach Plexus GIT motor
b. Meissners plexus regulate secretory activity of GIT
Can regulate activities GIT activities but ENTERIC activities are regulated by SNS and PNS.
SYMPA postganglionic fibers will synapse with GIT neurons. Indirectly innervates the organs of the GIT.
SYMPA stimulation will decrease GIT motor and secretory activities
PARASYMPA preganglionic fibers that will synapse with the Enteric NS (like a peripheral ganglion).
PARASYMPA stimulation will increase GIT motor and secretory activities
SNS
PSNS
Thoracolumbar division

Craniosacral division

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

1.
Innervates

Location of the Peripheral Ganglion


(See Fig. 15.2 15.3 of Tortora)

Originate from the spinal cord (T1-L3)

T1-T2: Head and Neck; smooth muscle of eye


and salivary glands
2. T3-T5: Thoracic region; heart, lungs and
bronchi
3. T6-T12: Enteric NS; stomach, small intestine,
proximal half of large intestine, liver, pancreas
and gall bladder
4. L1-L3: distal half of large intestine, rectum,
anus, genitourinary system
5. T1-L3: sweat glands and the vascular smooth
muscle
SYMPATHETIC AND PREVERTEBRAL GANGLIA
Near the center and far from effector cells
1. sympathetic chain - 22 pairs of ganglion
(beside vertebral column: paravertebral
location)

Superior cervical ganglion

Middle cervical ganglion

Stellate ganglion
2. collateral ganglia -3 pairs of ganglion
(Abdominal/pelvic region, in front of vertebral
column: prevertebral)

Celiac ganglion

Superior mesenteric

Inferior mesenteric

1.
2.

1.

TERMINAL GANGLIA
A. Ganglia far from the center but near the
effector cells
1. III Oculomotor: celiary ganglion: smooth muscle
of the eye
2. VII Facial:
a.
pterigopalatine ganglion: nasal and
lacrimal glands
b. Submandibular ganglion: submandibular
glands
3. IX Glossopharyngeal: otic ganglion: parotid
glands
B.
4.

Length
Branching of Preganglionic fibers

Neurotransmitter Agent
Locations where NTAs are released
Steps in Biochemical Transmission

CPalafox (1A)

Ganglia far from the center and inside the


effector cell
X Vagus, Sacral parasympathetic nerves (pelvic
nerves) a.
Vagus nerve:

Thoracic cavity (heart, lungs, bronchi)

Abdomen (Esophagus, stomach, small


intestine, proximal half of the large
intestine, Liver, pancreas, gall bladder)
b. Pelvic nerves: Distal half of large intestine,
rectum, anus, genitourinary system

Preganglionic fiber < Postganglionic fiber


Short Pre Long Post
Extensive branching
1 Pre : 20post
Sympathetic effects are more widespread and
diffuse

1.
2.
1.
2.
1.

Cholinergic Transmission mediated by Acetylcholine (Ach)


Noradrenergic or Adrenergic transmission by Norepinephrine (Nor)
Somatic Efferent : NMJ
Autonomic Efferent: region of peripheral ganglion and neuroeffector junction
Synthesis and Storage of neurotransmitter agent synthesis in the ribosomes; stored in secretory
vesicles
Release of NTA at the synaptic cleft motor impulse reaches nerve ending; highly permeable to Calcium
ions (influx); interaction of membrane proteins - Syntaxin and synaptobrevin cause vesicles to fuse
with nerve terminal membrane; exocytose the NTA into the synaptic cleft
Interaction - NTA binds with receptors and elicits a physiologic response from effector cell
Deactivation of NTA unbinding from the receptor
Ligand-activated / Ion channels
2. G-Protein coupled receptor
NTA + Receptor Opens specific ion channels
NTA + Receptor activate G-proteins bound to
a.
If Na+ channels, Na+ influx, depolarization
the inner surface of the cell membrane
will lead to excitation
 Activate specific intracellular (I/C) enzymes
b. If K+ channels, K+ efflux, hyperpolarization
that will lead to formation of intracellular
will lead to inhibition
ligands (aka Second Messengers), which
c.
If channels are on effector cell, elicit an
will mediate the action of the NTA on the
immediate but short-lived response from
effector cell.
the effector cell.
 Produces a delayed response but longer
Ex. Ach binding to nicotinic receptors on
duration that persists even if NTA is no
membrane of skeletal muscle cell 
longer present
Ach+Nicotinic: Ligand-gated channel
a.
NTA + Receptor activate G-Proteins 
activate enzyme system, (+) Adenylyl
cyclase  formation of cAMP (cyclic

2.

INTERACTION STEP / Membrane Receptors

Some originate from brain stem (CN III, VII, IX, X)


Some originate from spinal cord (S2-S4)

3.
4.
1.

Preganglionic fiber > Postganglionic fiber


Long Pre Short Post
Limited branching
1Pre : 1Post
PS Effects are more localized except those of the
vagus nerve

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

b.

Deactivation of NTA

Cholinergic transmission is present in:

Adrenergic transmission is present in:

adenosyl monophosphate is the I/C ligand


or second messenger)  activate (+)
protein kinase A  phosphorylation of
other enzymes that will elicit specific
responses from the cell
Ex. Catecholamines (Nor, EP) + beta
receptors;
Acetylcholine + muscarinic receptors
beta receptors and muscarinic receptors
are G-protein coupled receptors
NTA + Receptor activate G-Proteins 
activate enzyme system, (+)
phospholipase C  breakdown of
phosphoinositol biphosphate PIP2,
forming 2 products:
i. Inositol triphosphate IP3 
increase I/C Ca2+; Calcium can
function as second messenger
ii. Diacyl glycerol DAG  (+) Protein
kinase C  causes phosphorylation
of I/C proteins  stimulate specific
biochemical responses from the cell
Ex. Catecholamines + alpha receptors;
Acetylcholine + muscarinic receptors
(depending on the location in the body)

Enzymatic deactivation - deactivation by enzymes in


the synaptic cleft
Ex. Ach deactivation by acetylcholinesterase
1. Cholinergic effects short in duration

Re-uptake
Ex. Deactivation of norepinephrine
1. After unbinding from the receptor
2. Actively transported back in the terminal but
will not be stored in vesicles. These will be
destroyed by monoamineoxidase
3. Other NEP: circulated in the blood and
transported to the liver, where NEP is
deactivated by enzyme catechol-O-methyl
transferase (COMT)
1. All somatic neuromuscular junction (Somatic to skeletal muscle)
2. All autonomic ganglia (all preganglionic to all postganglionic in both SNS and PSNS)
3. All parasympathetic neuroeffector junctions (all PS effects to internal organs; biochemically, PSNS is
referred as Cholinergic division; PSNS division is craniosacral (anatomically) and cholinergic
(biochemically))
4. Sympathetic cholinergic neuroeffector junctions, only if effectors are sweat glands and vascular smooth
muscles present in skeletal muscles.
5. All sympathetic adrenergic neuroeffector junction. (all sympathetic effects to internal organs)
Sympathetic division is thoracolumbar (anatomically) and noradrenergic (biochemically).
Somatic NS
Parasympathetic NS
Sympathetic Cholinergic
Sympathetic Adrenergic
(Syncholinergic) NS
(Synadrenergic) NS
C

Ach

EC

Ach
PG

PG
Ach

Ach
EC

Ach
EC

** Only in sweat glands and


vascular smooth muscles
present in skeletal muscles

Cholinergic Transmission

CPalafox (1A)

Ach
PG
NEP
EC

** most sympathetic effects


to internal organs are
mediated by NEP

Transmission mediated by Acetylcholine


1. Synthesis of Acetylcholine: Choline + Acetyl CoA  Ach, catalyzed by choline acetyl transferase. It will be
stored temporarily in vesicles located at the nerve ending.
2. (Release) When an AP reaches the nerve ending, there will be Ca2+ influx, which will cause Ach to be
released into the synaptic cleft.
3. (Interaction) Ach binds to membrane receptors (cholinergic receptor) on the effector cell.
4. (Deactivation) Main mechanism is enzymatic destruction/deactivation by acetylcholinesterase, which is

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

also present in the synaptic cleft, where it can immediately deactivate acetylcholine. This makes
cholinergic or Parasympathetic effects short in duration.
1. Nicotinic can also be stimulated by small dose 2. Muscarinic can be stimulated by small doses
of nicotine
of muscarine
a.
Present in all somatic neuromuscular
a.
all parasympathetic neuroeffector junction
junction (membrane of skeletal muscle
b. all sympathetic cholinergic neuroeffector
cells contain Nicotinic receptors)
junction (sweat glands, vascular smooth
b. Present in all autonomic peripheral
muscle present in the skeletal muscle
Subdivided into M1-M5:
ganglia
c.
c.
Mainly made of proteins, classified as

M1 brain, stomach (if M1 receptors


Ligand-gated receptor: (+)  open Na+
in stomach is stimulated, increase in
channel
gastric secretion)
d. Always elicits an excitatory reaction

M2 most abundant heart and


visceral smooth muscles

M3 visceral smooth muscles and


glands

M4 visceral smooth muscles and


glands

M5 least abundant; present only in


sphincter muscles of the iris,
esophagus, parotid glands, cerebral
blood vessels
d. G-protein coupled receptor  response
may be either excitatory or inhibitors
Transmission mediated by NEP
1. Synthesis of NEP:
a.
Steps:
phenylalanine  tyrosine, catalyzed by phenylalanine hydroxylase.
tyrosine  DOPA, catalyzed by tyrosine hydroxylase.
DOPA  Dopamine, catalyzed by DOPA decarboxylase.
Dopamine  Norepinephrine, catalyzed by dopamine -hydroxylase.
b. Location: at the nerve ending of sympathetic adrenergic efferent / postganglionic nerve endings.
c.
Regulation: by a negative feedback mechanism; if there is an excess of dopamine and
norepinephrine, it will cause inhibition of the enzyme tyrosine hydroxylase.
d. A sagittal section of adrenal glands reveals 2 parts:
outer part: adrenal cortex (secretes steroid hormones) and
inner part: adrenal medulla (converts norepinephrine epinephrine, catalyzed by
phenylethanolamine-N-methyl transferase).
e. Sympathetic adrenergic postganglionic nerve endings can synthesize/release NEP only.
Adrenal medulla can synthesize/release both NEP and EP (collectively known as catecholamines).
2. (Release) When an AP reaches the nerve ending, there will be Ca2+ influx, which will cause NEP to be
released into the synaptic cleft.
3. (Interaction) NEP or EP binds to membrane receptors (noradrenergic or adrenergic receptors) on the
effector cell.
4. (Deactivation) Main mechanism is reuptake. Actively transported back in the terminal but will not be
stored in vesicles. These will be destroyed by monoamineoxidase. Other NEP: circulated in the blood and
transported to the liver, where NEP is deactivated by enzyme catechol-O-methyl transferase (COMT).
This makes adrenergic or Parasympathetic effects short in duration.

Types of Cholinergic receptors

Adrenergic Transmission

4 Types of Adrenergic receptors

1.

1
a.

2.

Organ
Heart
CPalafox (1A)

4.

2
a.
b.

3.
Present in visceral smooth muscles and
glands

Present only at nerve terminal


NEP+ 2  NEP inhibition
Negative feedback mechanism, inhibit
further release of norepinephrine
Alpha receptors when stimulated, mostly elicit
excitatory reaction (exemptions below)
Examples:
 NEP+ 1 Radial muscle of iris, muscle
contracts (excitatory) = increase in
pupillary size;
 EP+ 1 vascular smooth muscle, muscle
contracts (excitatory) = vasoconstriction
Exemptions: Digestive system, pancreatic
islets, bronchial gland, effects are inhibitory
Cholinergic
M2

1
a.
Only in heart
2
a.
Present in visceral smooth muscles and
glands
Beta receptors when stimulated, elicit mostly
inhibitory reaction (exemptions below)
Examples:
 NEP + smooth muscle receptors in
Bronchial wall, smooth muscles relax =
broncodilation;
 EP+ 2 Vascular smooth muscle, muscle
relaxes = vasodilation
Exemptions: heart, bronchial glands, pancreatic
islets, effects are excitatory

Adrenergic:
1

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

Salivary glands
Intestinal wall
Bronchial
Adrenal Medulla:
Differentiate from other visceral organs in
the body:
Difference from the rest of the
sympathetic adrenergic system:

M3-M4
M2-M3-M4
M3-M4
Sympathetic: innervated by postganglionic fibers
Sympathetic adrenergic: release NEP to immediate
vicinity of neuroeffectors

1, 2
1, 2
1, 2
Adrenal Medulla
AM is innervated by pre-ganglionic fibers.Cells of AM
are histologically similar to a sympathethic ganglion

When the sympathetic division is stimulated,


the AM is also stimulated, which causes it to
release NEP and EP. These NTA are released and
circulated in the blood stream, and are
distributed to sympathetic neuroeffector
junctions in all parts of the body.

Reinforces/potentiates the sympathetic


adrenergic effects.

AM considered a part of sympathetic adrenergic


nervous system
Sympathetic preganglionic fibers
Ach

(N) Adrenal Medulla


NEP + EP ***
Circulation
(+)1, 1, 2 receptors ***
sympathetic adrenergic effects
*** Comparison between the effects of NEP and EP

NEP is a strong stimulator of and 1 receptors


but is a weak stimulator of 2.

EP is a strong stimulator of 1, 1, 2 receptors.


Dual Innervation and Antagonistic Effects

Physiologic/Functional Differences
between Sympathetic and
Parasympathetic Nerves
Energy
Duration

Effects

CPalafox (1A)

Sympathetic NS and PSNS are PHYSIOLOGIC ANTAGONISTS, produces opposite effects.

1.

Dual innervation of the SAME structure of the SAME organ produces OPPOSITE effects.
Ex. Heart
Sympathetic N (HR)  SA Node Vagus/CNX, Parasympathetic (HR)

2.

Dual innervation of 2 DIFFERENT structures in the SAME organ produces OPPOSITE effects.
Ex. Eyeball Pupil regulates the amount of light entering the eye
Iris: radial muscle (Sympathetic): absence of light  pupil dilates
Sphincter muscle (Oculomotor CN3 parasympathetic): presence of light  pupil constricts

3.

Dual innervation of 2 DIFFERENT structures in the SAME organ produces SYNERGISTIC effects.
Ex. Salivary gland
Para: profuse increase in salivary secretion: loose, watery secretion
Sympa: mild moderate increase in salivary secretion: viscous secretion

4.

Single innervations
No parasympathetic innervation. Sympathetic innervation only.
Ex. Kidneys, sweat gland, pilo arrector muscle in skin, vascular smooth muscle
SyNS
PSNS

Catabolic
Longer, Prolonged duration
Reason: Norepinephrine at NEJ that is not
immediately deactivated; additionally
mediated by norepinephrine and epinephrine
in the blood stream
Fight-or-Flight
Stimulation of sympathetic nerves enables
individuals to cope or withstand stressful
conditions

Anabolic
Short duration
Reason: Mediated by Ach, immediately
deactivated

Rest/Digest
Conservation/restoration of the bodys
processes

Physiology A: AUTONOMIC NERVOUS SYSTEM


Lectured by: Dr. Valerio

Fight-or-Flight (Catabolic)
HR
BP

Nor

Epi

Response

Timing

Center

Rest/Digest (Anabolic)
HR
BP

Peripheral Vasoconstriction

M2,
M3

Peripheral Vasodilation

Ach

Lipid Breakdown

Lipid Breakdown

Coronary Dilation
Bronchial Dilation

Bronchoconstriction

Glycogen  Glucose

Generalized, diffuse response


Reason: extensive branching of the preganglionic fibers
Coordinated; response occurs at the same time

Muscarinic receptor
Nicotinic receptors

M3

M3

Glucose Glycogen

Localized response, except for Vagus nerve


Reason: limited branching, except for Vagus
nerve
Coordinated; but some processes do not have to
occur at the same time (ex. micturation, defecation,
erection)

Head ganglion of the ANS Hypothalamus

Anterior hypothalamus coordinates


Cholinergic activities

Posterior/ Lateral hypothalamus


coordinates Adrenergic activities
Example: Baroreceptor Reflex
Increased Arterial Blood Pressure (ABP)  stretch arterial walls
 (+) Baroreceptor  (-)/inhibit Vasomotor center (medulla)

Decrease sympathetic outflow

Increase parasympathetic outflow

Vasodilation

Decrease cardiac activity

Decrease cardiac activity

Decrease ABP

Decrease ABP
Pharmacological Differences
A.

B.

CPalafox (1A)

Parasympathetic
Cholinergic
/ Potentiate cholinergic or parasympathetic
effect
synthesis of Ach
release of Ach
interaction between Ach and cholinergic
receptor
(-) deactivation of Ach
PARASYMPATHOMIMETIC mimics the effects
of parasympathetic stimulation
Anticholinergic
/ Block cholinergic or parasympathetic effect
synthesis of Ach
release of Ach
Block interaction between Ach and cholinergic
receptor
inactivation of Ach
PARASYMPATHOLYTIC

A.

B.

Sympathetic Adrenergic
Adrenergic
/ Potentiate adrenergic or sympathetic effect
synthesis of NEP
release of NEP
interaction between NEP and adrenergic
receptor
(-) inactivation of NEP
SYMPATHOMIMETIC mimics the effects of
sympathetic stimulation
Antiadrenergic
/ Block adrenergic or sympathetic effect
synthesis of NEP
release of NEP
Block interaction between NEP and adrenergic
receptor
deactivation of NEP
SYMPATHOLYTIC

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