Transcript Neuroendocrine

Neuroendocrine function and
Hypothalamic control
Neuronal regulation (e.g., of
the cardiovascular system);
what is the point?
• CV system regulates quite well with no
neuronal input. Heart beat regulated by
intrinsic pacemakers and arteriolar constriction
regulated by local agents and circulating
hormones.
• At rest that is fine, but when the organism is
challenged, then there is a need to alter overall
CV output and local circulation.
Parallel pathways
regulate arterial
pressure, but their
time constants are
very different.
Blood volume
• Intake – output.
• Regulated by Aldosterone, Angiotensin,
Atrial Natriuretic Peptide, Vasopressin,
etc.
• Kidney main organ regulating volume
homeostasis.
It’s the flow
that is
important
Regional
blood flow is
important
and acute
changes in it
are largely
regulated by
the nervous
system.
What are the ultimate
neuronal controls of blood flow
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Sympathetic nervous system (NE+)
Parasympathetic nervous system (Ach+)
Circulating hormones
Locally released hormones
Local neuronal and glial regulation in the brain
Feedback control of nervous
system regulation of CV system
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Baroreflexes
Chemoreceptors
O2/CO2 receptors
Pain
exercise
Stretch
Heat
Nutrition
Baroreflexes
High pressure receptors in the aorta and
carotid artery
Low pressure (cardiopulmonary receptors)
atria
Both the IX and X
nerves carry
baroreceptor
information to the
brain. Other
baroreceptors located
throughout the body
organs, but their
influence is less
global.
Variability of AP
control without
baroreceptor
feedback.
Chemoreceptors
• Especially sensitive to O2 and CO2
CNS regulated neurohormones in
CV control
SNS activates renin release in
the kidney
• Renin in the circulation converts
anagiotensinogen to A I and ACE
converts AI to vasoactive AII.
• Also regulated by plasma ions (esp.
NaCl)
• Local AII system in brain and kidney
and heart.
Renin-Angoiotensin/nervous
system interplay
promotes vasoconstriction via
• Directly acting through AT1 receptors on
arterioles
• Increasing presynaptic release of NE
from sympathetic nerves
• Blunting baroreflex restraint
• Activating circumventricular organs, esp.
SFO and AP to increase SNS activity
and drinking and regulates vasopressin
Vasopressin
(AntiDiuretic Hormone; ADH)
• Released into the circulation by neurons in
the hypothalamus
• Circulating AVP elicits vasoconstriction via
V1 receptors and induces antidiuresis via v2
receptors in the kidney
• Also alters baroreflex and tonic control of
SNS activity by direct release from neurons
and circulating AVP diffusing to neurons
CNS controls Norepinephrine (NE) &
Epinephrine (Epi) release, but these
catecholamines have different actions
• Beta-adrenergic receptors have much higher
affinity for Epi << NE, while alpha-AR have the
opposite affinity.
• Beta-AR (vasodilatory) numerous on heart and
arterioles in heart and skeletal muscle
• Alpha-AR much more prominent on peripheral
arterioles and vasoconstrict.
• Stimulation of adrenal medulla increases heart
and skeletal muscle related vasodilation and HR.
Unlike an injection of NE
which raises BP and HR
via alpha1-AR equally,
epinephrine injections act
primarily on beta-AR
increasing HR/contractility
and thereby increasing
CO. BF is increased to
the skeletal muscle heart
and brain but decreased
to the kidney and skin.
TPR is reduced as
reflected in decrease in
diastolic pressure.
Increase in CO reflected
in increased systolic
arterial pressure.
VII. Autonomic Nervous System
Integrated
Neurendocrine
regulation of the CV
system
Brain areas involved in
neuroendocrine and
autonomic regulation
Rostral Ventral Lateral Medulla
(RVLM)
• RVLM generates sympathetic tone.
• Appears that the RVLM vasomotor
neurons are final integrators of a large
amount of information relative to CV
control.
Sensory regulation of RVLM via
nucleus of the solitary tract (NTS)
• Both high and low pressure
baroreceptor feedback to the brain
synapses in the NTS
• Gustatory and other inputs also reach
NTS in discrete regions
• The NTS has widespread projections to
forebrain and medulla
NTS
AP
Brainstem BP
control
pathway
ANGIOTENSIN
Higher control
I.
Hypothalamus (Head autonomic ganglion)
Hypothalamus
Optic chiasm
Fig. 1.3
Hypothalamus as Homeostatic Regulator
Parent, 17.1
A.
Vegetative function of hypothalamus;
regulation of eating, drinking and digestion
Parent, Fig. 17.1
Areas that receive information about warmth
Preoptic area
Anterior hypothalamic area
Parent, 17.1
Sympathoinhibitory nuclei
• Warm receptors
– Activation leads to inhibition of SNS
• Sweating
• Vasodilaiton
• Pyrogens bind here and allow fever to continue
by changing setpoint
• Renal excretion
• Drinking regulation (defending against
dehydration and overheating)
Circadian rhythm
• Suprachiasmatic nucleus
– Sets rhythm of AP/HR
– Daily blood pressure rhythm can be over
30 mmHg and reduction in nighttime dip is
sign if potential organ damage
– Normal rhythm is slightly over 24 hours,
but this is entrained by light to the eye
– Interesting regulation via sympathetic
innervation of pineal gland, thereby
releasing melatonin
M ean A r t er ial P r essur e ( mm H g)
160
140
120
1 00
80
60
40
24
12
24
12
24
Clock Hour
12
24
12
24
Circadian rhythm
Circadian output of SCN via
sympathetic nervous system
Regulates melatonin release from the
pineal
Which modulates sleep and sex
B. Activating nuclei to respond to cold or stress
Shut down eating/peristalsis
Shiver
Renal inhibition
Vasoconstrict non-required vascular beds
Increase blood flow to skeletal muscle
Parent, 17.1
Sympathoexcitatory nuclei
PHA
• Direct projection to the spinal cord
• May provide direct hypothalamic
modulation of CV system
• Cold sensors (defense of body heat)
– Vasodilation
– Shivering
Sympathoexcitatory nuclei
VMH
• Important in the defense/escape
reaction and also in eating and sexual
activity
Sympathoexcitatory nuclei
LHA
• Homeostatic regulator
– Leptin, glucose and insulin receptors
Monitoring inner world
Circumventricular organs
• Organum vasculosum of the lamina terminalis
(OVLT)
– sodium and osmotic sensitivity
• Subfornical organ (SFO)
– Angiotensin II
• Area postrema (AP)
– Toxin monitoring
D.
Endocrine control
Parent, Fig. 17.20
Circulating Neuroendocrine Elements
Parent, 17.1
Paraventricular (PVN) and supraoptic nucleus
Vasopressin
Oxytocin
Hormone regulators
Circulating hormones
Fig. 11.16
E.
Anterior lobe controled by arcuate nuclei,
e.g., sexual function, etc.
Parent, 17.20, 17.1
Interactions of neuropeptides and other
transmitters in autonomic control
Natriuretic peptide family
• ANP causes inhibition of NE release in CNS
and PNS (i.e. it acts opposite of AII).
• In PNS cause reduction in AP and increased
diuresis/natriuresis
• In hypothalamus it causes the opposite
effects.
• Regional distribution of ANP and receptors
underlie this effect. ANP inhibition of NE
throughout the hypothalamus causes
differential effects.
Sex steroids and
Vasopressin/Oxytocin
• SON/PVN
• Increases dendritic activation (electrical
and chemical) by juxtaposing the
dendrites.
• Regulation of fluid volume, memory,
sex, etc.
Beer Stories
• Drink beer; lots of beer fast
• About 30 minutes later need to urinate
badly
• Why??
• What happens if you keep drinking?
Beer Potomania
• Potomania: An intense and persistent
desire to drink alcohol to excess.
• Dilutional hyponatraemia
• Pass out/death
Why?
• Decrease ADH (vasopressin) as much
as possible in first hour
• Continue ingestion of fluid low in solutes
and lack of protein intake
• Decrease in plasma Na and osmolality
• Kidneys can only excrete limited load
Young individual can excrete up to 25 L/day about 1.2
L/hour, but when intake is increased above that level
dilution will occur first in vascular space and then in
extracellular and intracellular space.
Result:
• intracellular dilution and dysfunction of
neurons and muscle.
VIII. Enteric Nervous System
Approximately 108 neurons = all spinal cord
neurons
Regulate peristalsis in gut
While parasympathetic input accelerates
parastalsis, sympathetic input inhibits it
The system is truly peripheral with only CNS
regulation of speed
Summary Points
• The hypothalamus regulates the autonomic
nervous system and neuroendocrine system
• The anterior parts of the hypothalamus increase
parasypathetic responses while the posterior areas
tend to activate sympathetic responses.
• The paraventricular nucleus directly releases
neurohormones into the blood
• Other hypothalamic sites release hormone
releasing/inhibiting substances that circulate to the
anterior lobe of the pituitary and other sites to
release/inhibit the active circulating hormone.
• Autonomic control is regulated by the joint actions
of the nervous system and circulating hormones