Physiology of the vasculature (1)

Question 1

Main reasons for relaxation of the blood vessels (therefore dilation?)

Answer 1

exercise, digestion, increased transport and nutrients to an organ, thermoregulation (increased body temperature causes vasodilation)

Question 2

Main reasons for constriction of blood vessels ?

Answer 2

• to reduce blood loss, decreased body temperature, dysfunction to artery wall/endothelium

Question 3

Main features of arteries and capillaries?

Answer 3

Arteries - move blood away from the heart, strong, muscular tunica media to allow pulsatile blood flow and expansion/relaxation of blood vessels

Capillaries - branch off the arteries to supply organ tissue - lumen one cell thick!! Drain back into the heart via the veins

Question 4

Qualities of the endothelium

Answer 4

Inner lining of the blood vessels, huge surface area. Dysfunction = CV disease!
Release factors which act on smooth muscle cells in the tunica media

Question 5

Artery wall anatomy - significance of each layer?

Answer 5

Tunica intima - thin innermost layer which is in contact with the endothelium
Tunica media - thickest layer (contractile) consisting of contractile smooth muscle cells. This layer determines contractility of vessels

Question 6

What is the glycocalyx?

Answer 6

Continuous coating of secreted carbohydrate and sugar chains that prevents interaction of the blood and endothelial cells.

Question 7

What happens to the glycocalyx that can result in disease?

Answer 7

Infection, inflammation, injury and damage from OXLDLs can cause shedding of the glycocalyx, which results in dysregulation at the level of the endothelial cells

Question 8

What happens when the glycocalyx is shed?

How can this result in M/I

Answer 8

This causes exposure of adhesion molecules which causes binding of neutrophils and platelets –> these differentiate into macrophages

Disturbed blood flow in vessels can cause an atherosclerosis to form

Question 9

What neurotransmitter molecules bind to receptors in healthy endothelial cells to activate cell signalling? What is their impact?

What else can cause this?

Answer 9

Histamine (5-HT), Ach, Bradykinin
Cause an increase in intracellular calcium signalling and activate the eNOS enzyme which produces NO from arginine.

This can also occur as a result of shear stress

Question 10

Stimulating molecules/ stimuli that act on healthy endothelial cells?

Answer 10

Stimuli that activate ECs:

• interleukin-1
• endotoxin (bacterial cell wall)
• thrombin (from platelets)
• disturbed blood flow act on receptors

Question 11

What is the impact of the stimulation of active endothelial cells by different stimuli?

Answer 11

• altered activation of smooth muscle cells
• increase endothelin-1 or ROS
• activate adhesion molecule VCAM-1, ICAM- expression at the cell surface
• IL-8 production
• COX-2 activity.

Question 12

Impacts of increased adhesion molecule expression from Endothelial cells and shedding of the glycocalyx?

Answer 12

• increased monocyte, neutrophil or platelet interactions with the endothelial cell,
• promotes transmigration across the artery wall and atherosclerosis
• Endothelin-1 is released from the cell, and acts on adjacent vascular smooth muscle cells

Question 13

Where is Ca2+ stored for smooth muscle contraction and how is it transported?

Answer 13

Ca2+ is contained in nM concentrations in resting cells, ATPase pumps Ca2+ into cells to store it?

Question 14

VSMC contraction – process?

Answer 14

1) Ca2+ enters via channel and forms complex with Calmodulin, activating MLCK
2) MCLK phosphorylates myosin to active form allowing interaction with actin stimulating contraction
3) myosin phosphatase removes P from myosin to convert back to inactive form

Question 15

Differences between smooth and skeletal muscle?

Answer 15

In smooth muscle, myosin MUST BE PHOSPHORYLATED to be active
In smooth muscle, myosin phosphatase is constistuatively active so the default state of muscles is relaxed

Question 16

Vascular smooth muscle Ca2+ channels - what are the different types?

Answer 16

Receptor - P2X
Voltage sensitive L type channels
Store operated TRP channels

Question 17

Impact of increased IP3 levels on skeletal smooth muscle?

Answer 17

Increased IP3 levels, activate receptors on the SR membrane to cause intracellular calcium release and then activation of the myosin phosphorylation-contraction pathway.

Question 18

Other than via Ca2+ channels, what else receptor types stimulate VSMC contraction and via what mechanism?

Answer 18

GPCRs - ligands include: 
Endothelin A/B
TP (prostanoid)
AT1 (angiotensin)
Histamine
Noradrenaline (a-AR)