Lecture 10: Vascular function 1

Question 1

Describe the smooth muscle distribution of pre and post capillary vessels:

Answer 1

Pre capillary vessels have far more smooth muscle that post.

Question 2

Describe the ANS innervation of the vascular beds:

Answer 2

Innervation: Post ganglion nerve processes characterised by regular swellings (Sympathetic adrenergic nerve terminals)

• Arteries and arterioles densely innervated
• Caps not.
• Veins sparsely innervated (but increases with size)

NB: Some organs have PSNS cholingergic innervation of precap. vessels. (gut?)

Question 3

Describe the pressure drop across the network:

Answer 3

• Large conduit art. have little drop
• Gradient drop across the small arteries and arterioles (a.k.a pre-cap resistance vessels) These create the variable resistance
• Cap, venules, and small veins contribute to SOME resistance

Question 4

What regulates the blood flow to vascular networks? in the physical sense? How does this change pressure dynamics?

Reference:
- Resistance
- Pressure gradient
- Hydrostatic pressure

Answer 4

• Coordinated alteration of the lumen of pre-cap resistance vessels
  -[Vasodilation drops resistance and increases blood flow. Vasoconstriction increases resistance and reduces blood flow.]

= Changed pressure across a network
= Increased pressure gradient across vessels with higher resistance
= Increased resistance upstream causes reduces hydrostatic pressure in caps b/c the energy is dissipated prev.

Conversely:
- Dilation of preacps, drops pressure gradient in them but increases blood flow and increase cap hydrostatic pressure.

Question 5

Where is most of the circulatory blood stored?

Answer 5

Small veins and venules

Question 6

What happens with venoconstriction?

• Pressure (VR and Cap)

Answer 6

Reduced capacity to store blood and increases effective driving pressure back to the heart. (Venous return)

Such changes influence post cap. resistance and thus cap. hydrostatic pressure.

Question 7

How does intravascular pressure also impact the fluid compartments?

Answer 7

Intravascular pressure distribution affects the movement between fluid compartments i.e

Cap pressure magnitude and direction of fluid movement is determined by balance of:
- Transmural gradients of hydrostatic and colloid osmotic pressure.

Question 8

What typically happens with fluid movement in the capillaries? When might this change?

Answer 8

• Fluid filtered at arterial end is normally absorbed at venous end.
  = Net fluid movement is little.

BUT constriction of pre-cap = inc. resistance, decreased flow and hydrostatic pressure = favours movement from interstital space to vascular compartment. Vasodilation does vice versa.

Question 9

Does vascular SM contain basal tone? Does it have pacemaker activity?

Answer 9

Yes, it has spontaneous activity.

Yes it has pacemaker activity and because cells are coupled this spreads.

Question 10

What does the small dimension of vascular smooth muscle mean?

Answer 10

They are effected significantly by the external environment i.e
- Metabolism
- Paracrine factors
- Hormones
- Autonomic nerves
- The endothelial layer also influences their activity

Question 11

What are the things that affect vascular smooth muscle?

Answer 11

Autoregulation:
- Myogenic control
- Metabolic control
- Endothelial control
- Flow induce vasodilation
- Neurohormonal control

Question 12

What is VSM autoregulation?

Answer 12

• Intrinsic tendency of an organ to maintain a constant blood flow despite changes in the perfusion pressure.

(perfusion pressure being arterio-venous delta)

i.e Even if venous pressure increase, there may be an increase of flow but it returns to steady state.(and vice versa)

The level of blood that is maintained is determined by its metabolic needs.

Question 13

Describe how the effectiveness of autoregulation varies between vascular beds:

Answer 13

• Cutaneous blood flow exhibits nearly not autoregulation
• Cerebral is tightly regulated, but this is limited to between 50-180mmHg. (true for all vascular beds but varies)

Question 14

What does reactive hyperaemia demonstrate?

Answer 14

• Links metabolism to blood flow
• If you occlude blood vessels for short periods of time, post release BF is elevated above pre-occlusion levels and this hyperaemia is maintained for for a period roughly proportional to the occlusion time.

Question 15

What do autoregulation and reactive hyperaemia reflect?

Answer 15

• Operation of local control
• Occurs in deinnervated vascular beds.

Question 16

What is myogenic control?

Answer 16

• An increase in transmural pressure acting in a BV = increased vascular contraction. (vice versa)
• Most potent in medium arterioles, small and medium veins.

Question 17

How is myogenic control hypothesised to work?

Answer 17

• Distension triggers depolarisation and contraction of VSM.
• Stretch sensitive ion channels.

Question 18

What is metabolic control when it comes to VSM? Where is it most potent?

Answer 18

• Metabolism produces vasoactive substances i.e Adenosine, osmolarity, CO2, K. (Varying mechanisms)
• They can induce vascular vasodilation.
• Their concentrations depend on rate of production and wash out. Thus varying effect)
• Most potent in pre-cap vessels.

Question 19

Describe the endothelial control of blood vessels: What are two examples:

Answer 19

• Produce a number of vasoactive substances in response to blood flow and likely endothelial deformation

i.e

NO = cGMP = Dec. Ca, Hyperpolarisation = Vasodilation

Endothelin: Ca channel agonist, alters ANS of VSM = vasoconstrictor

Question 20

What does the myogenic, metabolic and endothelial mechanisms fail to explain?

Answer 20

They dont explain the vasodilation that occurs rapidly in proximal pre-capillary blood vessels, when tissue metabolism is increased. (i.e metabolic explains distal microcirculation dilations etc but not upstream)

Thus there must be additional pathways that signal upstream.

Question 21

Describe the proposed integrated model of local control:

Answer 21

• Metabolites dilate the microcirculation beds
• This increases flow and the increased flow signals upstream to dilate these precapillary vessels.
• Furthermore, ATP release from Hb when they are reduced is posited to release a ‘wave of endothelial electrical activity that causes vasodilation’. Hypothesis of course.

Question 22

What are the vascular mechanisms of the venous vessels?

Answer 22

• Vasodilator metabolites have little effect
• Vascular pressure and thus myogenic response facilitates constriction and enhanced venous return.

Question 23

Overview of the neurohormonal control of vascular function:

Answer 23

• Neurotransmitters act on vessels of circulating hormones bind to receptors on vascular smooth muscle of endothelium and induce an effect

Question 24

Describe how sympathetic adrenergic nerves cause vasoconstriction:

Answer 24

• NE main neurotransmitter, but co-transmitters i.e ATP and NPY are stored in vesicles and released.
• NE -> Gprotein (a1) or a2 = Vasoconstriction

NB: Increased cAMP = Vasodilation because it activates PKA which sequesters Ca.

Question 25

How is adrenergic stimulation regulated?

Answer 25

By the number of regulatory receptors in the nerve terminal membrane.

i.e Alpha 2 exist on presynpase to close the Ca channels (vesicle release) stops NE release and stabilises conc. (autoregulation)

Also modulated presynaptically by:
-Dec: Ach, adenosine, dopamine, histamine, PG-E1&2.
- Inc: ANG2 and Adrenalin

Question 26

Where might PSNS vasodilation occur?

Answer 26

Pre-cap vessels to the heart, brain. face. tongue, uro-genital

Question 27

How does the PSNS work?

Answer 27

ACh binds muscunaric receptors and causes NO release.

Question 28

Describe the effects of circulating catecholamines:

VIP

Answer 28

Huge difference between circulating noradrenaline and adrenalin.

Noradrenalin = Widespread vasoconstriction except coronary and cerebral. (A1, pre and post cap distribution)

Adrenalin causes same effects EXCEPT it causes vasodilation in muscle and splanchnic circulations. (B2 receptors facilitate this and have weak affinity for NE, also muscle and splachnic have only B2 in pre caps, no alpha)

Question 29

What other hormones effect the vasculature?

Answer 29

Vasoconstrictors: ANG2 and ADH