DRUGS ACTING ON

AUTONOMIC NERVOUS SYSTEM

 The nervous system is divided into two parts:
 the central nervous system (CNS) → the brain and spinal cord.
 the peripheral nervous system →(PNS) all afferent (sensory) neurons and efferent
(motor) neurons,
 The peripheral efferent system is further divided into
 the somatic nervous system →innervates skeletal muscle cells
 the autonomic nervous system → innervates three types of effector cells:
1. smooth muscle,
2. cardiac muscle, and
3. exocrine glands1.
 somatic nervous system can function
 on a reflex basis,
 voluntary control of skeletal muscle is of primary importance
 the autonomic nervous system
 voluntary control can be exerted,
 but reflex control is paramount2.
 the function of the autonomic nervous system is to maintain the constancy of the internal
environment (homeostasis).This includes
 the regulation of the cardiovascular system,
 digestion,
 body temperature,
 metabolism, and
 the secretion of the exocrine glands.

1
A gland that secrets their products through ducts opening on to epithelium rather than directly into the bloods
2
More important than anything else
ANATOMIC DIFFERENCES BETWEEN THE SOMATIC AND AUTONOMIC NERVOUS SYSTEMS
SOMATIC AUTONOMIC
 innervate skeletal muscle cells  innervate smooth muscle, cardiac
muscle, and exocrine glands
 axon leaves the CNS and travels without  two neurons are required to connect
interruption to the innervated effector the CNS and a visceral effector cell
cell  preganglionic and post ganglionic
neurons
 Nerve fibres Myelinated  Pregang.—myelinated
 Postgang.—non-myelinated
 Primary efferent transmitter  Primary efferent transmitter
acetylcholine acetylcholine, Noradrenaline
 Effects on target tissue-excitatory only:  Effects on target tissue - excitatory or
muscle contracts inhibitory
 Summary of function - posture and  visceral function, including
movement  movement in internal organs and
secretion;
 control of metabolism
 Neurotransmitter/receptor at  acetylcholine/muscarinic receptoror
neurontarget synapse-  noradrenaline/ - or β-adrenergic
 acetylcholine/nicotinic receptor receptor

 ANS together with the endocrine system controls the body's internal organs.
 It innervates
 smooth muscles,
 cardiac muscle ,
 glands ,
 controlling the circulation of blood ,
 activity of the G.I . Tract and
 body temp .
  the ANS can be divided into two
 sympathetic and - stimulate activities of the effect or organs (except digestive
organs)
 parasympathetic branches - inhibit activities of the effect or organs (except
digestive organs)


 The preganglionic neurons of the sympathetic nervous system →thoracolumbar division.

 The preganglionic neurons of the parasympathetic division have their cell bodies in the
brainstem and in the sacral →the craniosacral division.
 cranial part of the parasympathetic nervous system innervates structures in the
 head,
 neck,
 thorax, and
 abdomen
 The cranial parasympathetic fibers leave the CNS in
 the oculomotor →CNIII
 facial →CNVII
 glossopharyngeal→CNIX
  vagus cranial nerves → CNX
 Sacral parasympathetic outflow arises from the S2 to S4 segments of the spinal cord 
 sacral division of the parasympathetic nervous system innervates the remainder of the
intestines and the pelvic viscera

 Sympathetic Nervous System

 Generally stimulates the effector organ (except in digestive tract)
 It is activated in emergencies, flight– or– fight reaction
 The pregangionic fibers → produce Acetylcholine and are called cholinergic fibers.
 Most postganglionic fibers produce norepinephrine (noradrenalin) and are called
adrenergic fibers (exceptions are the sweat glands and blood vessels in skin).
 Innervation of thermoregulatory sweat glands is anatomically sympathetic but the
postganglionic nerve fibers are cholinergic and release acetylcholine as the
neurotransmitter
 Location of ganglia is within a few cm of CNS, along the vertebral column
 Sympathetic fibers originate from the thoracolumbar region of the spinal cord (T1 – L2).
 Short preganglionic fibers.
 Long postganglionic fibers.
 THERE is exception: A few sympathetic ganglia lie near the organs innervated (e.g.,
urinary bladder and rectum); thus, these preganglionic fibers are long and the
postganglionic fibers are short.
 The adrenal medulla, anatomically considered a modified ganglion, is innervated by
sympathetic preganglionic axons.
 the sympathetic nervous system is designed to produce widespread physiological
activity
 Postganglionic fibers are distributed throughout the body.
 preganglionic fiber branches a number of times after entering a ganglion and makes
synaptic connection with a number of postganglionic neurons.
 activity in a single sympathetic preganglionic neuron may result in the activation of a
number of effector cells in widely separated regions of the body
 When the sympathetic integrative centers in the brain are activated (by anger, stress, or
emergency), the body’s resources are mobilized for combat or for flight.
 Stimulation of the sympathetic nervous system results in
  acceleration of the heart rate and an increase in the contractile force of the heart
muscle.
 Increased blood flow (vasodilation) through skeletal muscle and
 decreased blood flow (vasoconstriction) through the skin and visceral organs.
 Activity of the gastrointestinal tract, such as peristaltic and secretory activity, is
decreased, and
 intestinal sphincters are contracted.
 The pupils are dilated.
 The increased breakdown of glycogen (glycogenolysis) in the liver produces an
increase in blood sugar,
 while the breakdown of lipids (lipolysis) in adipose tissue produces an increase in
blood fatty acids; → these biochemical reactions make energy available for active
tissues.

 Parasympathetic division
 Generally inhibits the effector organ (except in digestive tract).
 All pre and postganglionic fibers product Ach and are cholinergic.
 Location of ganglia (terminal ganglia) is in or near effector organ
 Pregarglionic fibers arise from
 CNS (brain stem) and
 sacral region of spinal cord (S2 – S4).
 Long preganglionic fibers.
 Short postganglionic fibers.
 with few exceptions, synapse on neurons in ganglia located close to or within the
innervated organ.
 Postganglionic fibers are limited to the
 head,
 viscera of chest,
  abdomen and
 pelvis.
 Parasympathetic innervation predominates over sympathetic innervation of
 salivary glands,
 lacrimal glands, and
 erectile tissue
 In general, a single parasympathetic preganglionic fiber makes a synaptic connection
with only one or two postganglionic neurons.
 parasympathetic preganglionic neurons influence only a small region of the body or
affect only specific organs.
 The parasympathetic nervous system is involved with the accumulation, storage, and
preservation of body resources.
 parasympathetic system is designed to function more or less on an organ system basis,
 For example,
 the activation of the gastrointestinal tract takes place during digestion of a meal;
 constriction of the pupil and
 accommodation for near vision are essential for reading.

 Neurotransmitters of the autonomic and

somatic nervous systems
(noradrenaline and adrenaline reffered in Europe and most of the world, in US norepinephrine and epinephrine)

1. Acetylcholine (ACh)

 ACh is released by exocytosis3 from nerve terminals.

 ACh is the neurotransmitter across
1. synapses at the ganglia of the SNS and PNS and
2. across synapses in tissues innervated by the PNS and
3. the somatic nervous system.
 ACh is not administered parenterally for therapeutic purposes because it is hydrolyzed
nearly instantly by butyrylcholinesterase.
 ACh release can be blocked by such drugs as botulinum toxin.
3
Fusion of secretory vesicles with the plasma membrane and result in the discharge of vesicle content in to the extracellular space.
 2. Norepinephrine and epinephrine

 are catecholamines
 released by exocytosis from nerve terminals at postganglionic nerve endings of the SNS
(except at thermoregulatory sweat glands, where ACh is the neurotransmitter).
 Norepinephrine release can be blocked by such drugs as
bretylium4 and guanethidine5.
 Norepinephrine and some epinephrine are released from adrenergic nerve endings in
the brain
 In the periphery, epinephrine, along with some norepinephrine, is the major
catecholamine released from adrenal medullary chromaffin cells into the general
circulation, where they function as hormones.

3. Biosynthesis of catecholamines

 In prejunctional nerve endings

 tyrosine is hydroxylated by tyrosine hydroxylase, the rate-limiting enzyme, to
form dihydroxyphenylalanine (dopa)
 dopa is then decarboxylated by dopa decarboxylase to form dopamine
 Dopamine is transported into vesicles, a step blocked by reserpine, where it is
hydroxylated on the side chain by dopamine b-hydroxylase to form
norepinephrine
 In certain areas of the brain and in the adrenal medulla, norepinephrine is
methylated on the amine group of the side chain by phenylethanolamine-N-
methyltransferase (PNMT) to form epinephrine.

 Tyrosine Dopa Dopamine

Dopamine
4
IS NOREPINEPHRINE RELEASE INHIBITOR USED FOR THE PROPHYLAXIS AND THERAPY OF VENTRICULAR FIBRILLATION AND LIFE
THREATENING VENTRICULAR ARRYTHMIAS.
5
ANTIHYPERTENSIVE AGENT USED IN THE MANAGEMENT OF MODERATE AND SEVERE HYPERTENSION, EITHER ALONE OR AS AN
ADJUNCT AND FOR THE MANAGEMENT OF RENAL HYPERTINSION.
 B-hydroxylase

Epinephrine Norepinephrine

4. Termination

 UPTAKE 1(reuptake 1) - carries norepinephrine back into the cell cytoplasm from the
synaptic cleft
 → inhibited by cocaine and tricyclic antidepressants (imipramine)
 → resulting in an increase of transmitter activity in the synaptic cleft

 Uptake 2 ( uptake 2)– active transport into extraneuronal cell

 Norepinephrine termination blocked by

 Cocaine
 Tricyclic antidepressants- imipramine
→ resulting in an increase of transmitter activity in the synaptic cleft

 Drug of abuse (cocaine) and antidepressants (desipramine, venlafaxine, reboxetine,

bupropion) block the transport of NE and thereby cause an elevation in synaptic
concentration of NE and potentiation of the activation of postsynaptic receptors.

Reserpine depletes norepinephrine from sympathetic nerve endings and blocks transport of

norepinephrine into storage granules, thereby reducing norepinephrine release into the
synapse after nerve stimulation.

 Norepinephrine is then transported by a second carrier system into storage

vesicles→blocked by reserpine
 Another active transport system (uptake 2) is located on glia 6 and smooth muscle cells
6
Also called glial cells (gliocytes) or neuroglia are non-neuronal cells in CNS and PNS, they maintain homeostasis form myelin in the
PNS and provide support and protection for neurons.
 5. TRANSMISSION OF THE NERVE IMPULSE

o “Swollen” areas found at intervals along the terminal axons are

referred to as varicosities.
o Within each varicosity are mitochondria and numerous vesicles
containing neurotransmitters
o vesicles are intimately involved in the release of the transmitter
into the synaptic or neuroeffector cleft
 NEUROTRANSMITTER RECEPTER
PREGAGLION ACn NICOTINIC
SYMPATHETIC ADRENAL
PREGAGLION ACn NICOTINIC
GLAND
POSTGANGLION NE ß, 
PREGAGLION ACn NICOTINIC
PARASYMPATHETIC
POSTGANGLION ACn MUSCARINIC
SOMATIC ONE NEURON ACn NICOTINIC
SYMPATHETIC ADRENAL ACn NICOTINIC
Neurotransmission in the PNS occurs at three major sites:  STEPS IN
(1) preganglionic synapses in both parasympathetic and sympathetic NEUROCHEMICAL
ganglia, (2) parasympathetic and sympathetic postganglionic TRANSMISSION
neuroeffector junctions, and (3) all somatic motor end plates on
skeletal muscle. o Fall types of neurons the fundamental
steps in chemical transmission are the
same.
o Each of these steps is a potential site for pharmacological intervention in the normal
transmission process:

o 1. Synthesis of the transmitter

o 2. Storage of the transmitter
o 3. Release of the transmitter by a nerve action potential
o 4. Interaction of the released transmitter with receptors on the effector cell membrane
and the associated change in the effector cell
o 5. Rapid removal of the transmitter from the vicinity of the receptors
o 6. Recovery of the effector cell to the state that preceded transmitter action

 Synthesis, Storage, Release, and Removal of Acetylcholine

o initial substrates for the synthesis of acetylcholine are glucose and choline
o Glucose enters the neuron by means of facilitated transport
o Choline is transported by a transporter protein in the membrane
o Pyruvate derived from glucose is transported into mitochondria and converted to
acetylcoenzyme A (acetyl-CoA).
o The acetyl-CoA is transported
back into the cytosol.
o acetylcholine is synthesized from
acetylCoA and choline by the
enzyme choline acetyltransferase
o acetylcholine is then transported
into and stored within the
storage vesicles
o Conduction of an action potential
through an axon →depolarization
of the varicosity membrane, →in
the release of transmitter
(exocytosis)
o A key factor in the process of
exocytosis is the entry of extracellular calcium ions during the depolarization.
o in the junctional extracellular space (biophase), acetylcholine interacts with
cholinoreceptors
o The interactions between transmitters and their receptors are readily reversible
o the number of transmitter–receptor complexes → direct function of the amount of
transmitter in the biophase
o acetylcholinesterase rapidly hydrolyzes acetylcholine in the biophase.
o Acetylcholinesterase highly concentrated on the outer surfaces of both the
prejunctional (neuronal) and postjunctional (effector cell) membranes.

o rapid hydrolysis of acetylcholine → lowering of the concentration → rapid dissociation

of the transmitter from its receptors

o little or no acetylcholine escapes into the circulation

o Any acetylcholine that does reach the circulation is immediately inactivated by plasma
esterases

 Synthesis, Storage, Release, and Removal of NOREPINEPHRINE

o Synthesis of norepinephrine begins with the amino acid tyrosine, →enters the neuron
by active transport.
o In the neuronal cytosol, tyrosine is
converted by the enzyme tyrosine
hydroxylase to dihydroxyphenylalanine
(dopa)
o Dopa converted to dopamine by the
enzyme aromatic L–amino acid
decarboxylase (dopadecarboxylase)
o dopamine is actively transported into
storage vesicles, where it is converted to
norepinephrine (the transmitter) by
dopamine β-hydroxylase, an enzyme within
the storage vesicle
o In noradrenergic neurons, the end product is norepinephrine
o In the adrenal medulla, the synthesis is
carried one step further by the enzyme
phenylethanolamine N-methyltransferase,
which converts norepinephrine to
epinephrine.
o the enzyme that converts dopamine to
norepinephrine (dopamine β-hydroxylase) is
located only within the vesicles,
o → the transport of dopamine into the
vesicle is an essential step in the synthesis
of norepinephrine.

o There is a tendency for norepinephrine to

leak from the vesicles into the cytosol
o If norepinephrine remains in the cytosol,
much of it will be destroyed by a
mitochondrial enzyme, monoamine oxidase
(MAO)
o However, most of the norepinephrine that
leaks out of the vesicle is rapidly returned to
the storage vesicles
 o Vesicular transport is from the neuronal cytosol across the membrane of the vesicle and
into the vesicle.
o It is important for a proper understanding of drug action to remember that this single
transport system, called vesicular transport, is an essential element of both synthesis
and storage of norepinephrine.
o the noradrenergic transmitter is released by action potentials through exocytosis,
o the formation of transmitter–receptor complexes is
 a direct function of the concentration of transmitter in the biophase and
 is readily reversible
o Three processes contribute to the removal of norepinephrine from the
biophase:

 Transport back into the noradrenergic neuron (reuptake)

 Diffusion from the synapse into the circulation
 Active transport of the released transmitter into effector cells (extraneuronal
uptake)

o 1. Transport back into the noradrenergic neuron (reuptake),

 followed by either vesicular storage or enzymatic inactivation by mitochondrial
MAO.
 Neuronal uptake is primarily a mechanism for removing norepinephrine rather
than conserving it.
 The transport of norepinephrine into the neurons is a sodium-facilitated process
similar to that for choline transport.
o 2. Diffusion from the synapse into the circulation
 ultimate enzymatic destruction in the liver and renal excretion.
 The liver has two enzymes that perform metabolism of NE : catechol-O-
methyltransferase (COMT) and MAO
 COMT is a specific enzyme, accepting only catechols7 as substrates
 The end result of the action of COMT is the O-methylation of the meta-hydroxyl
group on the catechol nucleus

7
substance with two adjacent hydroxyl groups on an unsaturated six-member ring.
o 3. Active transport of the released transmitter into effector cells (extraneuronal uptake)
 followed by enzymatic inactivation by catechol-O-methyltransferase

o norepinephrine or epinephrine in the circulation will equilibrate with the junctional

extracellular fluid and thus become accessible both to
 the receptors and
 to neuronal transport.
o Neuronal transport occurs from the junctional extracellular fluid (biophase) across the
cell membrane of the neuron and into the neuronal cytosol
o The neuronal transport system is the most important mechanism
 for removing norepinephrine
 for limiting the effect and duration of action of norepinephrine or epinephrine,
whether these are released from the adrenal medulla or are administered as
drugs.

o RECEPTORS ON THE AUTONOMIC EFFECTOR CELLS

o Acetylcholine will not interact with receptors for norepinephrine (adrenoceptor), and
norepinephrine will not interact with cholinoreceptors.
o These receptors are selective not only for their respective agonists but also for their
respective antagonist drugs→
 drugs that antagonize or block acetylcholine at cholinoreceptors will not
antagonize norepinephrine at adrenoceptors and vice versa.
o Cholinoceptors
o CHOLINOCEPTORS- bind acetylcholine with high affinity and trigger intracellular changes
influencing the behavior of cells.
o The action of administered acetylcholine on effector systems innervated by
parasympathetic postganglionic neurons
 smooth muscle cells,
 cardiac muscle cells, and
 exocrine gland cells resembled the actions produced by the naturally occurring
plant alkaloid muscarine

o The actions of both acetylcholine and muscarine on the visceral effectors are
similar to those produced by parasympathetic nerve stimulation.

o →The effects of acetylcholine on visceral effectors as the muscarinic action

o →The receptors are called the muscarinic receptors

o Muscarinic receptors are localized on numerous autonomic effector cells

 including ;
 cardiac atrial muscle and cells of the sinoatrial (SA) and atrioventricular (AV)
nodes,
 smooth muscle,
 exocrine glands, and vascular
 endothelium (mostly arterioles), /although does not receive parasympathetic
innervation/
 certain areas in the brain.

o The administration of acetylcholine mimics the stimulatory effect of nicotine, the

alkaloid from the tobacco plant, on autonomic ganglia and the adrenal medulla.
o Acetylcholine effect on autonomic ganglia and adrenal medulla referred as the nicotinic
action
o →receptors are nicotinic cholinoreceptors or nicotinic receptors
 Nicotinic receptors- Cholinoceptors that are activated by the alkaloid nicotine
 localied at
 junctions of somatic nerves and skeletal muscle
  autonomic ganglia
 adrenal medulla
 certain areas in the brain.
 In skeletal muscle, ACh interacts with nicotinic receptors results muscle
contraction

o The action of acetylcholine at the skeletal muscle motor end plate resembles that
produced by nicotine.
o → the cholinoreceptor on skeletal muscle is a nicotinic receptor.
o Based on antagonist selectivity, however, the autonomic and somatic nicotinic receptors
are not pharmacologically identical

o ADRENOCEPTORS

o ADRENOCEPTORS- receptors that are target of catecholamines like

 Norepinephrine
 epinephrine - the adrenal medullary hormone
 a number of chemically related drugs
o On the basis of the observed selectivity of action among agonists and antagonists, it was
proposed that two types of adrenoceptors exist
o Designated as
 - adrenoceptors (1 and 2)
 β-adrenoceptor (β1 and β2)
o The 1-adrenoceptors are located at postjunctional (postsynaptic) sites on tissues
innervated by adrenergic neurons (Sympathetic)
o Activation of 1-adrenoceptors in smooth muscle of blood vessels leads to
vasoconstriction
 o 2-Adrenoceptors having a presynaptic (i.e.,neuronal) location

 1-adrenoceptors→ postjunctional (postsynaptic) of adrenergic neurons

 β2-adrenoceptors → bronchial smooth muscle & blood vessels of skeletal muscle →
relaxation - vasodialation
 1-adrenoceptors → activation on blood vessel→ vasoconstriction
 β1-adrenoceptors → cardiac tissue → ↑heart rate contractile force

o The β1-adrenoceptors are found chiefly in the heart and adipose tissue,
 Activation of β1-adrenoceptors on cardiac tissue produces an increase in the
heart rate and contractile force.
o while β2-adrenoceptors are located in a number of sites, including
 bronchial smooth muscle and
 skeletal muscle blood vessels, → associated with smooth muscle relaxation.
 Activation of β2-adrenoceptors in blood vessels of skeletal muscle
produces vasodilation
o Norepinephrine and epinephrine are potent -adrenoceptor agonists,
o Norepinephrine and epinephrine are thus potent vasoconstrictors of vascular beds that
contain predominantly -adrenoceptor
o Isoproterenol and epinephrine are potent β2-adrenoceptor agonists;
o norepinephrine is a relatively weak β2-adrenoceptors agonist.
o isoproterenol8, a synthetic adrenomimetic, is selective for β1- and β2-adrenoceptors
→has little effect in these vessels
o Isoproterenol, epinephrine, and norepinephrine are potent β1-adrenoceptor agonists;
thus, all three can stimulate the heart

8
ALSO KNOWN AS ISOPRENALINE - DRUG USED TO TREAT BRADYCARDIA (HEART BEAT<60 BPM)
 Receptors of the nervous system

1. CHOLINOCEPTORS- bind acetylcholine with high affinity and trigger intracellular changes
influencing the behavior of cells.

 Hydrolysis of ACh by AChE results in muscle cell repolarization

 The selective nicotinic receptor antagonists tubocurarine and trimethaphan can
block the effect of ACh at skeletal muscle and autonomic ganglia, respectively.

 Muscarinic receptors consist of at least 3 functional receptor subtypes (M1–M3).

 Muscarinic M1-receptors are found in sympathetic postganglionic neurons

and in CNS neurons;
 M2-receptors are found in cardiac and smooth muscle; and
 M3-receptors are found in glandular cells (e.g., gastric parietal cells), and the
vascular endothelium and vascular smooth muscle.
 M2- and M3-receptors predominate in the urinary bladder.
 All three subtypes are found in the CNS.
2.
 INNERVATION OF VARIOUS ORGANS BY THE SYMPATHETIC
AND PARASYMPATHETIC NERVOUS SYSTEMS

 Many neurons of both divisions of the autonomic nervous system are tonically active;
that is, they are continually carrying some impulse traffic.

 BLOOD VESSELS
o Most vascular smooth muscle is innervated solely by the sympathetic (noradrenergic)
nervous system
o EXCEPTIONS:
o Some blood vessels in the
 face,
 tongue, and
  urogenital tract (especially the penis) are innervated by parasympathetic
(cholinergic) as well as sympathetic (noradrenergic) neurons.
o parasympathetic innervation of blood vessels has only regional importance
o primary neural control of total peripheral resistance is through sympathetic nerves
o The diameter of blood vessels is controlled by the tonic activity of noradrenergic
neurons.
o by the tonic activity of noradrenergic neurons →continuous outflow of noradrenergic
impulses→ some degree of constant vascular constriction is maintained
o increase in impulse outflow →contraction of the smooth muscle, →greater
vasoconstriction.
o A decrease in impulse outflow →smooth muscle to relax→vasodilation.

 THE HEART
o innervated by both sympathetic and parasympathetic
neurons → however, their distribution in the heart is
quite different
o Postganglionic noradrenergic fibers (sympathetic) from
the stellate and inferior cervical ganglia innervate
 the sinoatrial (S-A) node9 and
 myocardial tissues of the atria and
ventricles.

o Activation of the sympathetic outflow to the heart results in an increase

 positive chronotropic effect → ↑in rate
 positive inotropic effect → ↑in force of contraction
 positive dromotropic effect → ↑in conductivity of the atrioventricular (A-V)
conduction tissue

o postganglionic cholinergic fibers of the parasympathetic nervous system innervate

 S-A node,
 atria, and
9
Specialized myocardial structure that initiates the electrical impulses to stimulate contraction. Continuously generates electrical
impulses thereby setting the normal rhythm and rate in the healthy heart. SA node is referred as the natural pacemaker of the heart.
  A-V conduction tissue.
 Cholinergic fibers do not innervate the ventricular muscle to any significant
degree.
o Activation of the parasympathetic outflow to the heart results in a
 Negative chronotropic effect →decrease in rate
 negative dromotropic effect → prolongation of A-V conduction time
 There is a decrease in the contractile force of the atria but little effect on
ventricular contractile force

o The effect of a drug on the heart depends on the balance of sympathetic and
parasympathetic activity at the time the drug is administered.

 CARDIOVASCULAR REFLEXES

o Baroreceptors are a type of mechanoreceptors allowing for relaying information derived

from blood pressure within the autonomic nervous system.
o Information is then passed in rapid sequence to alter the total peripheral resistance and
cardiac output,
o Maintaining blood pressure within a preset, normalized range.

o There are two types of baroreceptors:

 high-pressure arterial baroreceptors and → located within the carotid
sinuses and the aortic arch
 low-pressure volume receptors, which are both stimulated by stretching of
the vessel wall.→ located within the atria, ventricles, and pulmonary
vasculature.
o Baroreceptors constantly monitor
 how much blood you have in your blood vessels and
 what the pressure is inside them.
 o When your blood pressure needs to change, your baroreceptors tell your brain. Your
brain signals your heart or blood vessels to take action that raises or lowers your blood
pressure
o The primary sensory mechanisms that detect changes in the mean arterial blood
pressure are stretch receptors (baroreceptors) in the
 carotid sinus
 aortic arch.10
o The injection of a vasoconstrictor, → an increase in mean arterial blood pressure, →
activation of the baroreceptors and increased neural input to the cardiovascular centers
in the medulla oblongata.→ an increase in parasympathetic nerve activity and a
decrease in sympathetic nerve activity. → This combined alteration in neural firing
reduces cardiac rate and force and the tone of vascular smooth muscle.
o The injection of a vasoconstrictor, → ↑ arterial blood pressure, → activation of the
baroreceptors → ↑ increased neural input to medulla oblongata.→ ↑ parasympathetic
nerve activity and → ↓in sympathetic nerve activity. → ↓ cardiac rate and force and
the tone of vascular smooth muscle→ ↓BP

 THE EYE

o Two sets of smooth muscle in the iris control the diameter of the pupil.
 dilator pupillae - set of muscles, which is arranged radially→, is innervated by
sympathetic (noradrenergic) fibers
 constrictor pupillae - is set of circular smooth muscle →is innervated by
parasympathetic neurons
o
o Sympathetic stimulation → contraction radial muscle → dilation of the pupil (mydriasis).
o Parasympathetic stimulation → contraction of the circular smooth muscle →
constriction of the pupil (miosis)
o The lens, which aids in visual accommodation, is attached at its lateral edge to the ciliary
body11 by suspensory ligaments.
o When the smooth muscles of the ciliary body are relaxed, the ciliary body exerts tension
on the lens, causing it to flatten.→ accommodated for far vision

10
THE aortic and carotid sinus have stretch fibers which send electrical signals to the brain based on how much stretch stimulus they
receive.
11
Found behind the iris and includes the ring shaped muscle that change the shape of the lens
o Stimulation of parasympathetic cholinergic neurons,→ causes contraction of the smooth
muscle of the ciliary body; this decreases the lateral tension on the lens→
accommodates for near vision
o Drugs that block accommodation are called cycloplegic
o blockade of parasympathetic neurons by atropine or of both autonomic systems by a
ganglionic blocking agent will result in
 pupillary dilation (MYDRYASIS) and
 a loss of accommodative capacity.

 Pulmonary Smooth Muscle

o innervated by both divisions of the autonomic nervous system

o stimulation of parasympathetic neurons → bronchoconstriction
o Sympathetic noradrenergic neurons appear to innervate vascular smooth muscle
o adrenoceptors are present on bronchial smooth muscle and that epinephrine from the
adrenal gland and drugs such as epinephrine and isoproterenol produce bronchodilation
of the airway.

 Gastrointestinal Tract
o stimulation of sympathetic noradrenergic neuron → inhibits
 gut motility and
 gland secretion and
 contracts sphincters.

 Salivary Glands
o One exception to the generalization that the two systems work in opposition to each
other is secretion by the salivary glands

o BUT the nature of the saliva produced by the two systems is qualitatively different.
 The saliva produced by activation of the sympathetic system is a sparse,
thick, mucinous secretion,
 produced by parasympathetic activation is a profuse, watery secretion

 THE ADRENAL MEDULLA

o The cells of the adrenal medulla, called chromaffin
cells,→are homologous with sympathetic
postganglionic neurons.
o The adrenal medulla secretes two hormones
 Norepinephrine (noradrenaline)
 Epinephrine (adrenaline)
o Activation of the sympathetic system → increased
secretion of adrenal medullary hormones, which
consist primarily of epinephrine in the human.
o Some blood-borne substances of endogenous origin,
such as
 histamine,
 angiotensin, and
 bradykinin, →can directly stimulate the chromaffin cells to secrete
epinephrine and norepinephrine.
o Exogenously administered drugs, such as cholinomimetic agents and caffeine, can
directly stimulate the secretion of adrenal medullary hormones.
o The neuronally induced secretion of medullary hormones is antagonized by ganglionic
blocking agents.