L11.3 Developmental origins of vascular dysfunction Flashcards Preview

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Flashcards in L11.3 Developmental origins of vascular dysfunction Deck (13):
1

What factors are altered which causes vascular dysfunction?

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

2

Structure of a vessel

  • 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

3

Endothelium dependent relaxation

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

4

3 vasodilation pathways

  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

5

Difference in vasodilation mechanism of different sized muscles?

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

6

How does birth size lead to endothelial function

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

7

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

  • 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

8

Wire myography

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

9

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

  • 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

10

Effects of maternal alcohol intake

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

11

Influence of lactational environment on vascular function in adulthood

  • Restore vascular function
  • Restore vascular vessel stiffness

12

Pressure myography

  • 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

13

Stress/strain curve created by pressure myography

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