Nervous and Hormonal Control of Circulation

Question 1

Give examples of Local Vascular control.

Answer 1

Local control involves the vessel itself such as: the myogenic response (ability of blood vessels to regulate diameter according to pressure across them), paracrine agents, nitric oxide, PGs and endothelin released from the endothelial cells. There are also physical factors such as temperature, pressure and you also have autoregulation (metabolic reactants/products affect blood vessels).

Question 2

Give examples of Extrinsic Vascular control?

Answer 2

Extrinsic control is ultimately controlled by the brain, which can alter blood flow selectively to organs when required e.g. exercise, sexual activity. Extrinsic controls are “outflows” from the brain, so these are.
• The release of neurotransmitters – e.g. vasoconstrictors (NA), vasodilators (Ach), nitric oxide (NO).
• Hormones (adrenaline, angiotensin II, vasopressin)

Question 3

Where does the Main Excitatory drive of the sympathetic vasoconstrictor system originate and where does the information come from?

Answer 3

Process starts in the rostral ventral lateral medulla (RVLM) which receives info from the CVLM (hypothalamus).

Question 4

The main excitatory fibres stimulate pre-ganglionic neutrons in the intermediolateral point. Where do these neutrons go?

Answer 4

Leave the spinal cord and enter the sympathetic ganglia, where they stimulate the post-ganglionic neurones, which go off to their target organs.
At the heart, NA is released acting at β1 receptors, at the blood vessels there is release of NA to α1 and at β2 receptors (beta receptors found in specific tissues like coronary circulation and skeletal muscle circulation).
They can also goto the adrenal medulla.

Question 5

What happens when the adrenal medulla is stimulated?

Answer 5

They stimulate the adrenal medulla to release adrenaline (small amounts of NA can be released from adrenal medulla also) that enters the circulation.

Question 6

Which layer of the blood vessel wall are the sympathetic fibres found in?

Answer 6

Tunica adventitia contains various structures but importantly contains the sympathetic vasoconstrictor fibres, these fibres come close to the tunica media (where VSMC’s are) and have special synapses called varicosities (like a pearl necklace).

Question 7

How does stimulation of a sympathetic fibre varicosity in the Tunica Adventitia lead to constriction of vessel?

Answer 7

vgCa2+ channels open and there is an influx of Ca2+. This triggers exocytosis of NA (with ATP), release of NA into the space where the smooth muscle cells are.
Primarily, the NA binds to α1 adrenoceptors which causes contraction of the muscle fibre.
NA can also act on other receptors on the smooth muscle, such as β2 receptors which causes relaxation of vascular smooth muscle, there is also α2 (for contraction) receptors which are located on the varicosity which act as regulation mechanism of how much NA is released (stimulation of them will reduce NA release), acting as a feedback mechanism.

Question 8

How does Angiotensin II cause vasoconstriction when binding to the pre-synaptic membrane of a sympathetic fibre in the Tunic Adventitia?

Answer 8

Binds to AT1 receptor and causes an increase in cAMP which increases the influx of Ca2+ ions and therefore causing increased NA vesicle release.

Question 9

Name substances which can cause vasodilation by reducing the release of NA from the sympathetic varicosity.

Answer 9

PGE1, Histamine, Adenosine, K+, Serotonin

Question 10

What are the 3 types of vasodilator nerves?

Answer 10

1. Parasympathetic vasodilator nerves
2. Sympathetic vasodilator nerves
3. Sensory (nociceptive C fibres) vasodilator fibres
   Vasodilatation occurs when vascular tone produced by sympathetic vasoconstrictor nerves is inhibited

Question 11

Where are parasympathetic vasodilator nerves found?

Answer 11

• Salivary glands to increase blood flow by releasing Ach/VIP as during parasympathetic response more saliva needs to be produced.
• The pancreas and intestinal mucosa are also secretory organs, so parasympathetic increases blood flow to these areas to produce more secretion (through VIP release).
• Innervate the genitalia (erectile tissue) by NO and VIP to produce erection. It is important to remember that the release of NO by parasympathetic nerves causes production of cGMP which leads to vasodilation.

Question 12

Where are sympathetic vasodilator nerves found and when are they ‘activated’?

Answer 12

Act at the skin, they increase sweating but alongside this they increase blood flow to allow more sweat to be produced. The nerves innervating the sweat glands are the sudomotor fibres which also innervate the blood vessels around them to dilate them and increase blood flow to produce more sweat (through Ach and VIP)

Question 13

What doe stimulation of nociceptive c fibres lead to?

Answer 13

Causes vasodilation of local blood vessels, this is important because the dilatation means more blood flow to the area, so more immune cells (which is what you want if you have a trauma of infection). If you have a trauma, you will feel pain and the AP will travel up the C fibre (nociceptive afferent fibre), down the main axon and through the dorsal root ganglion where it will give the sensation of pain.

Question 14

What is Lewis Triple Response?

Answer 14

Local redness
Wheal
Flare
This explains why trauma causes redness, swelling also happens due to the blood vessel (capillary) permeability increasing giving local oedema. This whole response, the C-fibre axon reflex, mediates the flare to trauma.

Question 15

Stimulation in C-fibres will result in stimulation of main axon collaterals. What does this lead to?

Answer 15

Release substance P (or CRGP) at the site of injury. Substance P can bind to the endothelium of blood vessels and produce vasodilatation or can bind to mast cells to stimulate histamine release, which also causes vasodilatation.

Question 16

List some vasoconstrictor hormones and how they work.

Answer 16

Adrenaline - a catecholamine secreted by the adrenal medulla.
Angiotensin II (Ang II) - Impotant in haemorrhage, increases in hypertension, controls aldosterone release.
Vasopressin (Anti-Diuretic Hormone, ADH) - Causes increased uptake of water in the kidneys, so important in hyaemorrhage (increase blood volume). Causes vasoconstriction at higher levels.

Question 17

Give the name of an important vasodilator hormone (released from heart).

Answer 17

Atrial natriuretic peptide (ANP) - Does the opposite to ADH, is a vasodilator and has diuretic effects (reduces blood volume), its levels are increased in cardiac failure.

Question 18

What is the difference between Adrenaline and Noradrenaline and why does this difference exist?

Answer 18

NA always produces vasoconstriction
A can produce vasoconstriction (in GI) or vasodilatation (skeletal muscle, coronary circulation) depending on the vascular bed. The reason for this difference is down to the A and NA’s affinities for adrenoceptors. Adrenaline has a higher affinity for β receptors over α adrenoceptors. Noradrenaline has a higher affinity for α over β adrenoceptors.

Question 19

What are some of the main roles of Adrenaline?

Answer 19

Involved in glucose mobilisation (liver glycogenolysis, fat lipolysis) – to provide energy source during exercise. It also provides stimulation of heart rate and contractility during exercise in normal humans.
Provides the stimulation of the heart in cardiac transplant patients (as the nervous supply to the heart has been removed), so they are completely reliant on A/(NA) from adrenal gland.

Question 20

What happens to the circulation and heart when patient is given IV Adrenaline?

Answer 20

Adrenaline has a higher affinity for Beta adrenoceptors. It binds to Beta 1 on the heart muscle causing an increase in HR and increasing CO. However, BP does not increase by much because the adrenaline acts on Beta 2 receptors causing skeletal muscle arterioles to dilate and this means that TPR decreases and so the effects are cancelled out.

Question 21

What happens to the circulation and heart when patient is given IV Noradrenaline?

Answer 21

Noradrenaline has a higher affinity for Alpha adrenoceptors. This means it will bind to Alpha 1 receptors and cause vasoconstriction in vessels, this greatly increases TPR. The increase in TPR stimulates baroreceptors located in the arch of the aorta and causes sympathetic stimulation of the heart to be ‘switched off’ this leads to a decrease in HR.

Question 22

What type of hormone is aldosterone and where is it released from?

Answer 22

Aldosterone is a mineralcorticoid hormone and it is released from the zona glomerulusa in the adrenal medulla.

Question 23

What are the 2 effects of ADH?

Answer 23

At high concentrations it is a potent vasoconstrictor. Its normal role however is as an anti-diuretic, increases reabsorption of water.

Question 24

How is ADH released and what stimulates the release of ADH?

Answer 24

ADH release can be stimulated by atrial baroreceptors (ABR) and/or the left atrial receptors (LAR). If there is a rise in blood pressure, the stretch receptors will be activated, this stimulates the nucleus tractus solitarius (NTS) in the brainstem. This switches off an inhibitory pathway between the NTS and CVLM. This leads to the pathway between the CVLM and hypothalamus (SON and PVN) being switched on.

Question 25

Where is ANP released from and what is its purpose?

Answer 25

ANP is released by specialised atrial myocytes released when pressure increases (when filling pressure gets too much). ANP causes vasodilation by acting at Natriuretic Peptide receptors on VSMCs. Through increasing a cGMP pathway (similar to NO).
Also decreases plasma volume. It does this latter by acting on the kidney. In the kidney we have afferent arteriole bringing blood to the glomerulus and the efferent arteriole bringing blood away from the glomerulus.
ANP acts at receptors found on the afferent arteriole, if you cause vasodilation here you will increase blood flow to the glomerulus.
The more blood flow to the more glomerulus, the greater the filtration rate, more filtration and there will be and more excreted. This decreases blood volume and thus decreases the filling pressure on the heart.