10. introduction to blood flow and regulation

Question 1

What is the endothelium?

Answer 1

Innermost layer of blood vessels

Question 2

What is the function of the endothelium?

Answer 2

Vasal tone control- vasocontrictors and vasodilators

Selective barrier

Angiogenesis

Inflammatory mediator production

Production of ecto-enzymes (clear cell membrane proteins away)

Question 3

What substances are produced by the endothelium?

Answer 3

EDRF

Prostacyclin

Endothelins

Antithrombin III

Plasminogen activator

VwF

Question 4

How is the endothelium involved in transport?

Answer 4

Hydrophilic- diffuse through pores

Lipophilic- active or passive transport

Endothelial structure helps role. Can be continuous, fenestrated or discontinuous

Question 5

What molecules are used as vasodilators?

Answer 5

Nitric oxide- requires elevated calcium

Prostacyclin- vasodilator

ADP- acts independently of endothelium

Question 6

What conditions are required for the release of nitric oxide?

Answer 6

Shear stress
Oxidant stress

Nitric oxide synthase- requires calcium and NADPH

Question 7

Describe the action of angiotensin II as a local vasoconstrictor

Answer 7

Endothelium has cpability to produce ecto-ace turning ANG I into ANG II.

ANG II Increases smooth muscle and contracts the muscle

Question 8

How does ACE have a synergestic effect to angiotensin II?

Answer 8

Inactivates bradykinin, removing a vasodilatary substance

Question 9

How is ANG II blocked?

Answer 9

Blocked by renin inhibitor,

ACE inhibitors

angiotensin I antagonists

Question 10

What are endothelins?

Answer 10

Potent and long lasting vasocontrictors

Released in response to stretchign vessels

Question 11

What is required for angiogenesis?

Answer 11

ECGF,

Appropriate conditions ( tumour, juvenile growth, regeneration)

Question 12

Name some pathological conditions that impact the endothelium

Answer 12

Xanthin dehydrogenase under ischameic conditions couric acid to xanthine which will damage the endothelium

Lack of NO can cause hypertension

Endothelin 1 has been found to be raised in some cases of hypertension

Question 13

How does smooth muscle control blood pressure?

Answer 13

Contracts in response to intracellular calcium

typically caused by action potentials

Question 14

How does the anatomical function of smooth muscle impact its function?

Answer 14

Sarcomplasmic reticulum allows for calcium storage

Gap juncitons allow for electricla coupling for co-ordinated contractions

Caveolae- invagination in surface increases surface area (?for calcium)

Question 15

Describe the process of caclium uptake storage and release from smooth muscle.

Answer 15

Calcium is pumped into cells through Serca 2a and 2b pumps

Calcium is held in cells via caclium binding proteins calsequestrin and calreticulin

Caclium is removed vie ryanodine receptors and more commonly IP3 receptors

Question 16

How does smooth muscle contract?

Answer 16

Phosphorylaiton of myosin causes binding to actin resulting in contraction of the cell

Question 17

How does phosphorylation of myosin occur?

Answer 17

An increase in calcium leads to calmodulin being released

Ca4 calmodulin acts as a secondary messenger which acts ipon myosin light chain kinase

This leads to phosphorylation of myosin light chains

Question 18

What is a kinase?

Answer 18

an enzyme that catalyses the transfer of a phosphate group from ATP to a specified molecule

Question 19

What is used to “switch off” muscle contraction

Answer 19

Myosin protein phosphatase

dephosphorylates myosin

Question 20

What is meant by excitation-contraction coupling?

Answer 20

Mechanisms which link initial stimulation to contractile activity in smooth muscle

Question 21

What are the two types of excitation coupling?

Answer 21

Electromechanicial- causes contractions by changing the membrane potential of the cell

Pharmacomechanical coupling- produces contraction with no changes in membrane potential

Question 22

Describe the physiology of electromechanical coupling and pharmacomechanical coupling?

Answer 22

Electromechanical : L-type calcium channels allow calcium in due to depolorisation. Potassium flows out

Noradrenaline allows g-proteins and GTP to cause an influx of calcium. IP3 also allows calcium to be released from the SR.

Question 23

How do you increase calcium in smooth muscle cells

Answer 23

Receptor operated channels- Activated by ligands

Voltage operated calcium channels activated by de-polorisation

Intracellular calcium activated by IP3