L11.3 Developmental origins of vascular dysfunction

Question 1

What factors are altered which causes vascular dysfunction?

Answer 1

• SM: controls vasodilation/vasoconstriction by contraction/relaxation
• Endothelium: secretes molecules for vasodilation/constriction
• Nerves
• Extracellular matrix and vessel stiffness

Question 2

Structure of a vessel

Answer 2

• Tunica intima
  
  • Endothelial cells → produce factors (i.e. NO) which directly acts on the vascular SM
• Tunica media
  
  • SM → able to contract/relax
• Tunica adventitia
  
  • Collagen → gives rigidity and structure of vessels
  • Elastin → ability of vessels to expand

Question 3

Endothelium dependent relaxation

Answer 3

• From ACh (Vasodilator) binding to MusR → triggers 3 vasodilation pathways

Question 4

3 vasodilation pathways

Answer 4

1. Production of NO
   
   • Triggered by eNOS (endothelial NO synthase) → NO → guanylate cyclase → acts on vascular SM → cGMP → hyperoplarisation → relaxation
2. PHGI
   
   • → adenylate cyclase → acts on vascular SM → cAMP → hyperpolarisation → relaxation
3. ↑Ca
   
   • → ↑K into vascular SM → Hyperpolarisation → relaxation

Question 5

Difference in vasodilation mechanism of different sized muscles?

Answer 5

• The bigger the vessel → the more reliant on NO
• The smaller ‘resistance vessels’ → all 3 vasodilation pathways involved

Question 6

How does birth size lead to endothelial function

Answer 6

• Measuring brachial A diameter using BF
• SGA babies → reduced response to Ach → ↑stiffness to vessels
  
  • Evidence of endothelial dysfunction

Question 7

How do we know the endothelium is dysfunctional and not the VSM?

Answer 7

• SGA 9yo →
  
  • Using Ach (acts on endothelium) → reduced response to ACh
  • Using nitroglycerine (acts on vascular SM) → normal response
    
    • Shows is endothelium dysfunction and not vascular SM dysfunction

Question 8

Wire myography

Answer 8

• Measure ability of BV to constrict/dilate to particular drug
  
  • Measure both endothelial and VSMC function

Question 9

SGA mother’s effect of F2 on VSM’s response to drugs

Answer 9

• SM response to vasoconstrictors
  
  • ↑sensitivity to U46619 vasoconstrictor
    
    • ↑risk of hypertension by ↑afterload
• SM response to SNP (NO donor - causing dilation)
  
  • Decreased sensitivity to SNP
  • Sensitivity can be restored through cross-fostering

Question 10

Effects of maternal alcohol intake

Answer 10

• ↑vascular stiffness
• ↓capacity to BF → ↑risk of hypertension

Question 11

Influence of lactational environment on vascular function in adulthood

Answer 11

• Restore vascular function
• Restore vascular vessel stiffness

Question 12

Pressure myography

Answer 12

• Determines arterial stiffness
• Mounted on glass canula → assess contribution of extracellular matrix to arterial function
  
  • Measuring ability of artery to expand under pressure
  • VSM is inhibited using ETGA

Question 13

Stress/strain curve created by pressure myography

Answer 13

• Relax = curve shift to right
• Stiff = curve shifts left