Regulation of Blood Flow and Blood Pressure

Question 1

The function of blood vessels

Answer 1

Carry blood around the body towards target organs and tissues

Question 2

Systemic arteries, arterioles and capillaries

Answer 2

carry oxygenated blood and nutrients from left ventricle towards systemic organs

Question 3

Systemic veins, venules, and capillaries

Answer 3

deoxygenated blood and waste from periphery towards the right atria

Question 4

Pulmonary blood vessels

Answer 4

• reoxygenation of blood at the lungs
• returned to heart for circulation

Question 5

function of intima (endothelial cells and subendothelial space)

Answer 5

• single-cell layer
• first barrier to pathogens in the blood
• communicates with vascular smooth muscle to regulate diameter

Question 6

function of the media (vascular smooth muscles)

Answer 6

relaxation/constriction dictates vessel diameter

Question 7

Adventitia/externa

Answer 7

• outer layer of fibrous connective tissue surrounding an organ
• collagen rich
• external elastic lamina
• vaso vasorum

Question 8

Vessel diameter

Answer 8

regulates blood flow and pressure

Question 9

Layers of arteries and arterioles

Answer 9

intimal, medial, and externa elastic

Question 10

Function of valves

Answer 10

Prevent backflow of blood

Question 11

Difference between veins and arteries and arterioles

Answer 11

veins and venules lack elastic layers

Question 12

Key hormones in regulation of vasular tone

Answer 12

• nitric oxide
• endothelial derived hyperpolarising factor
• endothelin-1
• angiotensin II

Question 13

Production of nitric oxide

Answer 13

• stimulation of GPCR by ligand creates multiprotein cascade
• production of IP3 which acts on the ER to singal release of intracellular calcium
• calmodulin activation -> phosphorylation and activation of nitric oxide synthase (ENOS)
• ENOS catalyses the conversion of L-Argenine to L-Citruline

Question 14

How does nitric oxide cause smooth muscle contraction

Answer 14

• activation of guanylyl cyclase
• converts GTP to GMP
• activation of PKG
• relaxation of muscle fibres

Question 15

Endothelial derived hyperpolarising factor (EDHF)

Answer 15

• hyperpolarises smooth muscle via stimualtion of potassium efflux
• muscle relaxation
• important when NO production is compromised
• acts predominantly at the arteriole level

Question 16

Endothelin-1

Answer 16

• acts on smooth muscle to induce vasoconstriction via smooth muscle intracellular calcium release
• inhibits eNOS
• reduces NO bioavailability
• promotes vascular inflammation

Question 17

Angiotensin II

Answer 17

• multiple tissue targets
• smooth muscle constriction via GPCR signalling and intracellular calcium release
• excessive levels promote high blood pressure and vascular inflammation

Question 18

Metabolic syndrome diagnostic criteria

Answer 18

• insulin resistance
  and any two of:
• obesity
• dyslipidaemia
• raised blood pressure
• raised blood glucose

Question 19

Atherosclerosis

Answer 19

progressive thickening and hardening of medium to large sized arteries as a result of fat deposition on the inner lining

Question 20

5 key stages of atherosclerosis

Answer 20

1. endothelial dysfunction
2. immune cell infiltration
3. fatty streak
4. young plaque
5. unstable plaque

Question 21

Endothelial dysfunction

Answer 21

• can be measured as indicator of atherosclerosis risk
• begins in response to cardiovascular risk factors and chronic inflammation
• loss of endothelium-derived vasomotor control (decreased NO production, increased ET-1)

Characterised by
- increased expression of adhesion molecules
- increased chemokine and cytokine secretion
- increased cell permeability
- increased LDL oxidation

Question 22

Immune cell infiltration

Answer 22

• infiltration of the sub-endothelial space by immune cells and ox-LDL

Characterised by
- increased adhesion molecules present on endothelial cells
- initial recruitment of monocytes/macrophages
- followed by other immune cells (T and B cells, neutrophils and dendritic cells)

Question 23

Fatty streak

Answer 23

• further accumulation of ox-LDL and phagocytosis of ox-LDL by macrophages
• visible as yellow fatty streak on vessel lumen
• lipid droplets form in vascular smooth muscle cytoplasm
• smooth muscle and fibroblast proliferation and migration
• dysregulated signalling of ET-1, NO, and Ang-II

Question 24

Young plaque

Answer 24

• accumulation of ‘foam cells’ and thinning of fibrous cap
• foam cells cluster, creating hypoxic central core (becomes neurotic)
• fibrous cap of developing plaque thins as lesion grows
• plaque is stable but narrowing vessel lumen

Question 25

Vulnerable/unstable plaque

Answer 25

- plaque becomes unstable - necrotic core - calcification - likely to rupture, releasing thrombus and occluding vessel

Question 26

How does adipocyte dysfunction promote atherosclerosis

Answer 26

- hyperinflammatory adipocytes release pro-inflammatory cytokines and adipokines - contribute alongside: insulin and leptin resistance, increased FFA, and hypercholesterolaemia

Question 27

Dysregulation of AngII in MetS

Answer 27

- increased levels and signalling - promotes inflammation and smooth muscle proliferation, resulting in atherogenic environment

Question 28

Dysregulation of ET-1 in MetS

Answer 28

- potent inflammatory peptide - promotes oxidative stress and immune cell recruitment in vessel wall - increased production and processing also supresses NO signalling, promoting vasoconstriction

Question 29

Dysregulation of NO in MetS

Answer 29

bioavailability of NO reduced via inhibition of eNOS and peroxinitrate production

Question 30

Dysregulation of EDHF in MetS

Answer 30

decreased production and transport of EDHFs, impairing vascular responses

Question 31

MetS and CVD

Answer 31

- pathophysiology of CVD and MetS is multifaceted - wide array of therapies to treat insulin resistance, inflammation, oxidative stress, cholesterol, hyperglycaemia, hypertension

Question 32

Common therapies for MetS and Atherosclerosis

Answer 32

- Thiazolidinediones (TZDs/Glitazones) - HMG-CoA Reductase Inhibitors (Statins) - AMPK activators (Biguanides) - Antioxidants

Question 33

Thiazolidinediones (TZDs/Glitazones)

Answer 33

PPARy agonists - insulin sensitisers - increases HDL cholesterol - anti-inflammatory effect in vessel wall

Question 34

HMG-CoA Reductase Inhibitors (Statins)

Answer 34

cholesterol biosynthesis inhibitors - increases HDL cholesterol levels - decreases LDL cholesterol levels and oxidation

Question 35

AMPK activators (Biguanides)

Answer 35

complex I inhibition - regulates glucose metabolism - increases FA oxidation - reduces inflammation

Question 36

Antioxidants

Answer 36

- reduce ROS - reduce LDL oxidation

Question 37

Current therapies for vascular dysfunction

Answer 37

- NO donors - ACE inhibitors - Endothelin receptor antagonists - Endothelin converting enzyme (ECE) inhibitors (currently untested in humans) - Surgery

Question 38

NO donors

Answer 38

Improves vasoresponsiveness

Question 39

ACE inhibitors

Answer 39

- reduces AngII production - alleviates vasoconstriction / favours vasodilation - reduces blood pressure

Question 40

Endothelin receptor antagonists

Answer 40

limited effectiveness