ANAT 322 Lecture Notes - Lecture 4: Neurotensin, Growth Factor, Adipose Tissue
7 Jun 2018
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ANAT 322 Winter 2017
Lectures
Lecture 4:
→ Biological Activities of Vasopressin
3. In spite of its name, vasopressin, which tells us that the original bioassay that led to the identification
of the hormone had to do with its function in increasing blood pressure. It also regulates water
retention in the kidney which is why it is also called antidiuretic hormone (ADH) and it is the only
endogenous anti-diuretic regulator in the body. Thus, the only mediator that increases anti-diuresis so if
the vasopressin system is malfunctioning it will result in diabetes insipidus (not mellitus) which results in
uncontrolled secretion of water through the kidneys which is life threatening. There are multiple other
substances that also regulate blood pressure so this is a redundant system but the anti-diuresis effect in
not redundant.
The triple diagram shows on the left axis increasing plasma osmolality values in milliosmoles which is
measured through the electrical conductivity of the liquid. The more diffusible, electrically charged ions
are dissolved in the liquid the more electrically conducive it becomes. This is plotted in parallel with the
plasma concentration of vasopressin, in the middle axis, in pictograms per millilitre (pg/ml). 280 mOsm
is the threshold where secretion of vasopressin will start and higher osmolality will lead to increasing
plasma vasopressin levels.
Increasing plasma osmolality means the organism is lacking waters so one of the physiological
reactions is water retention in urine in the kidneys to minimize the loss of water. The curve on the right
plots the concentration of osmolality of the urine that is being produced in the kidney and therefore its
volume. With high levels of vasopressin we get very concentrated urine with low volume whereas as the
vasopressin gets lower, we have higher volumes of urine being produced per day. If no vasopressin then
we will have diabetes insipidus and large volumes of urine are produced and secreted which is life-
threatening.
Circumventricular organs are those where the blood brain barrier is open through presence of
fenestrated capillaries and two come into place in the regulation of vasopressin; the subfornical organ
(SFO) and the organo vasculosum of the lamina terminalis (OVLT). They have neurons that are sensitive
to plasma osmolality and are therefore conductivity sensors. These are two sensors that would be
involved in the regulation of this regulatory system that would signal to vasopressin neurons if blood
osmolality is going up and more vasopressin needs to be secreted.
If we lack water, we lack volume of blood and blood pressure goes down which constitutes a second
stimulus for vasopressin release among other substances. This information is picked up by
baroreceptors in the vascular system found for example in the aortic arch and the information will be
conveyed through the CNS by the 9th and 10th cranial nerves (CN).
4. Information from peripheral baro- and osmoreceptors coming through the CN relay the information
to the nucleus of the solitary tract (NTS) in the brainstem. From there the sensory information goes to
the base of the brainstem to A1 noradrenaline neurons which will extend their long axons to the
magnocellular neurons in the parvocellular nucleus (PVNm) where they will release noradrenaline (NE).
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ANAT 322 Winter 2017
Lectures
On the other hand, information about blood osmolality comes is relayed via neurons located in the
circumventricular organs (OVLT and SFO).
5. Schematic depiction of the nephron, the functional unit of the kidney, with the glomerulus, the
descending and ascending ducts, the loop and the collecting ducts that will go to the marrow of the
kidney which is a mechanism that allows passive concentration of primary urine. At the glomeruli, there
is ultrafiltration that results in the primary urine being made which is then transported to the collecting
ducts and then to the marrow of the kidney.
The end concentration of urine is determined by insertion of water channels in the apical membrane
of the epithelial cells there called aquaporins. Vasopressin is the main regulator of aquaporin insertion in
the apical membrane so more vasopressin means more aquaporins that results in more reabsorption of
water from the primary urine in the collecting tubules.
6. Both water shortage and bleeding will lead to reduction in blood pressure. If we are in hypovolemic
conditions and thus there is decrease blood volume, that will lead to much faster and stronger increase
or secretion of vasopressin. This will result in a higher resorption of water in primary urine but also in
increase in blood pressure. The green line in diagram (N) represents normal blood volume in an adult
human.
7. There are two amplifying mechanisms increasing vasopressin release as a result of a reduction in
blood volume or blood pressure:
1. Via the baroreceptors in the vascular system, this will lead into the activation of neurons in NTS in
the brainstem that will stimulate A1 neurons that will in turn project to the PVN and SON to excite
vasopressin neurons there.
2. The other major and most potent regulator of blood pressure is plasma angiotensin II and its
increase will be sense in the SFO and that will also stimulate the PVN and SON.
8. Angiotensin precursor is called angiotensinogen and is produced in the liver and circulates in the
body. The enzyme that will convert angiotensinogen into a functional hormone is renin that is produced
in a group of cells in the glomeruli of the kidney that reacts to reductions in blood pressure.
Renin will cleave angiotensinogen and liberate angiotensin II that has effects on the brain that will
lead to an increase in vasopressin that increases blood pressure. Immediately, it will also have effects on
the vascular system (smooth muscle cells and vessels) and will lead to vasoconstriction and increase in
blood pressure. It will also cause increases in epinephrine and norepinephrine (E and NE) release as well
as adrenaline and noradrenaline (A and NA) from sympathetic terminals which will also cause increase
blood pressure.
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ANAT 322 Winter 2017
Lectures
Vasopressin is one of the players in this whole system being recruited by angiotensin action with it
being the main player.
→ Plasticity in the Magnocellular System
9. Vasopressin seems to be a hormone important in emergency situations for the organism. The same
thing goes for the oxytocin system which is the major regulator of smooth muscle that plays a major role
during childhood and lactation that do not occur too often. Every now and then the system needs to
secrete these hormones in non-emergency conditions and it achieves this through plasticity at the level
of the hypothalamus.
10. Mechanisms described for oxytocin neurons in the PVN and SON.
At baseline activity levels (left panel), there is some oxytocin being released but there are few active
synapses of sensory neurons onto the cell bodies of these oxytocin neurons. The neurons themselves
are separated by intermediate nervous tissue filled with glial cells or their processes and they are thus
insulated from one another.
During lactation, the neuronal cell bodies appear to touch so there are no interfering elements
between cell bodies and the number of synapses are higher.
11. This is a process that can happen within hours and the reason being the capacity of glial cells (in
grey) or more specifically astrocytes, which produce lots of processes that fill the spaces, to retract and
move the processes.
In magnocellular areas of the hypothalamus when the magnocellular system becomes active, these
retract so many more axon terminals that are sitting there can contact the neighbouring cell bodies and
they establish contact to one another. If one cell gets excited by neuronal input then this excitation will
spread faster to the whole system and recruit whole groups of neurons to quick into high activity.
12. Another mechanism that has been shown in magnocellular neurons during lactation is the increase
in dendritic release of secretory granules near the oxytocin cell bodies as can be seen in the lower panel
with dark stained circles. These neurons carry oxytocin receptors which are auto-receptors on their own
dendrites and cell bodies that will contribute to their continued excitation in a situation in which strong
stimulation is coming in. A similar mechanism also happens with vasopressin and auto-receptors.
This has been first described for magnocellular neurons in the PVN and SON but similar mechanisms
have also been found in the arcuate nucleus that contains parvocellular neurons. This appears to be a
more general principle in some functional systems of the hypothalamus where the astroglia and auto-
receptors play a role in the regulation of the activity of the nucleus. These are two mechanisms of
plasticity that allow the further increase in its activity when required.
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Document Summary
Biological activities of vasopressin: in spite of its name, vasopressin, which tells us that the original bioassay that led to the identification of the hormone had to do with its function in increasing blood pressure. It also regulates water retention in the kidney which is why it is also called antidiuretic hormone (adh) and it is the only endogenous anti-diuretic regulator in the body. Thus, the only mediator that increases anti-diuresis so if the vasopressin system is malfunctioning it will result in diabetes insipidus (not mellitus) which results in uncontrolled secretion of water through the kidneys which is life threatening. There are multiple other substances that also regulate blood pressure so this is a redundant system but the anti-diuresis effect in not redundant. The triple diagram shows on the left axis increasing plasma osmolality values in milliosmoles which is measured through the electrical conductivity of the liquid.
