Endothelial Cell Physiology And Control Of Vascular Tone

Question 1

Where is the endothelium located?

Answer 1

• tunica intima
• endothelial cell lining & connective tissue
• internal elastic lamina

Question 2

What are functions of the endothelium?

Answer 2

• control of vasal tone = produces both vasoconstrictors and vasodilators
• selective barrier = transports water, lipids, gases, proteins, passive diffusion, active transport
• angiogenesis = growth of new capillaries
• maintenance of fluidity = anti-thrombosis & monitors sheer stress
• inflammatory mediators = platelet adhesion, prostacyclins
• ecto-enzymes = ace, anti-thrombin III, nucleotidases

Question 3

What are substances produced by the endothelium?

Answer 3

• EDRF = endothelium derived relaxing factor = major vasodilator
• prostacyclin = PGI2 = inhibitor of platelet aggregation, a vasodilator
• adenosine = vasodilator
• endothelins = potent vasoconstrictors
• anti-thrombin III = anti-clotting agent
• plasminogen activator = TPA = anti-clotting agent, via the stimulation of fibrinolysis
• von willebrand factor = facilitates platelet adhesion

Question 4

Nitric Oxide - NO - what does it do?

Answer 4

• soluble, highly reactive gas
• produced by animal and plant cells
• produced from the amino acid L-arginine
• can diffuse through cell membranes
• used as a biological signal

Question 5

What does nitric oxide do in mammals?

Answer 5

• helps maintain blood pressure
• assists the immune system in killing invaders
• role in brain development
• role in neurone to neurone signalling
• helps form memories

Question 6

EDRF:

Answer 6

• released in response to an agonist, sheer stress & oxidant stress
• constrictive nitric oxide synthase (NOS) = calcium ion, calmodulin & NaDPH requiring enzyme
• activation = via inducible NOS
• which is cytosolic

L-arginine
- NADPH
- CA2+ & Calmodulin
- Citrulline released
- NOS catalyses
NO

Question 7

Endothelial vasoconstriction:

Answer 7

• endothelium prompts vasoconstriction
• due to the expression of ecto-ACE
• this converts angiotensin I to angiotensin II
• causes the release of endothelin I
• which results in vasoconstriction

Question 8

Angiotensin II:

Answer 8

• associated with renin-angiotensin system
• renin cleaves angiotensin to angiotensin I

Question 9

What produces ACE? = Angiotensin Converting Enzyme

Answer 9

• pulmonary and renal endothelium

Question 10

ACE:

Answer 10

• circulating angiotensin I is converted to angiotensin II locally
• angiotensin II binds angiotensin receptors on vascular smooth muscle
• increases the calcium ion levels, causes contraction of the muscle
• ACE degrades & inactivates bradykinin
• removing a vasodilator signal
• ACE inhibitors are widely used to treat hypertension

Question 11

Summary of renin-angiotensin aldosterone system:

Answer 11

• liver produces angiotensin
• kidney produces renin
• renin converts angiotensin to angiotensin I
• ACE converts angiotensin I to angiotensin II
• angiotensin II = sympathetic activity increases, na+ absorption, k+ excretion, water retention, more aldosterone is secreted to help this
• vasoconstriction, increase in blood pressure
• ADH secretion, water absorption

Question 12

Endothelin I:

Answer 12

• family of 4 related short peptides
• vasoactive constrictor peptide
• acts via endothelin receptors in vascular smooth muscle
• evokes muscle contraction and vasoconstriction
• acts due to shearing forces = positive = angiotensin II, thrombin & NO & prostacyclin = negative

Question 13

Angiogenesis:

Answer 13

• new blood vessels can be produced if needed
• regeneration during disease or injury
• juvenile growth
• tumorigenesis

Question 14

How the endothelium is triggered to generate a new capillary:

Answer 14

• fibroblast growth factor = involved in cell growth
• vascular endothelial growth factor = angiogenesis stimulator
• angiotensin I & 2 = helps stabilise the new vessel
• matrix metallo-proteases = degrades vessel walls

Question 15

Angiogenesis process:

Answer 15

• new capillary branch is required
• endothelial cell divides
• vacuoles form between new cells
• vacuoles join up to form lumen of new capillary

Question 16

What happens if angiogenesis is excessive:

Answer 16

• cancer
• aids complications
• psoriasis
• blindness
• rheumatoid arthritis

Question 17

What happens if not enough angiogenesis occurs:

Answer 17

• infertility
• ulcers
• heart disease
• stroke

Question 18

Transport role of endothelium:

Answer 18

• thin singular layer of cells
• intercellular spaces & pores allow molecular & fluid transport
• pore diameter is varied by contraction of actin & myosin cytoskeleton
• hydrophilic substances diffuse through the pores
• lipophilic compounds dissolve in cell membranes, they are carried actively or passively

Question 19

Pinocytosis

Answer 19

= important transport mechanism of very small molecules

Question 20

Clotting role of endothelium:

Answer 20

• endothelial cells line the blood vessels
• damage to the blood vessel = incomplete endothelial layer
• allows blood to exit the vessels

Question 21

Blood exiting vessels = allows platelets to interact with:

Answer 21

• tissue factor
• van willebrand factor
• this causes platelet activation

Question 22

What happens when platelets are activated?

Answer 22

• they plug the gap in the endothelial layer
• this allows damage to be repaired
• platelets & blood clots disperse
• and fix the damage in the endothelial layer

Question 23

A healthy endothelium should produce?

Answer 23

Clotting factors

Question 24

What are the clotting factors it should produce?

Answer 24

• tPA = tissue plasminogen activator
• anti-thrombin III