Endothelium
7 important questions on Endothelium
How does flow-mediated dialation (FMD) work to measure endothelial dysfunction?
ECs respond to shear stress (increased blood flow) by producing NO -> vasodilatation
Use high resolution ultrasound scanner to monitor and record vessel diameter changes.
Use blood pressure cuff to create flow stimulus: deflation causes blood flow to rise, causing shear stress and dilation. FMD is % of diameter increase from baseline to max. post-cuff deflation diameter.
After rest/return to baseline diameter, sublingual glyceryl trinitrate (GTN) is given. Max. diameter after GTN reflects smooth muscle intergrity, and is the max vasodilator response.
What are disadvantages of FMD?
- difficult to reproduce
- intra-/inter-observer variability
- time consuming
- movement participant
What is angiography, and how is it used to measure endothelial dysfunction?
Injecting a radio-opaque contrast agent in the blood, using X-ray for imaging.
Use acetylcholine to induce NO production and vasodilatation.
Invasive and complex, so only used in research.
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How is a polyphenol-rich able to improve endothelial function?
Polyphenols in fruits, vegetables, tea, chocolate, red wine. Antioxidant activity, reduce oxidative stress.
- reducing excessive NADPH oxidase-dependent vascular oxidative stress
- increase endothelial NO formation
- increase EDHF-mediated responses
Why is the efficiacy of polyphenols limited in humans?
1: bioabsorption in gut, blood and brain is very low
2: maximum plasma levels flavonoids 1-3h after consumption
3: half-life flavonoids only a few hours
4: extensively metabolised in liver and intestine (and brain), unable to reach endothelium
How is L-arganine involved in endothelial function?
Main substrate for NO production by eNOS. In milk, beef and soybeans.
NADPH oxidation can be uncoupled from NO generation, leading to superoxide formation.
Low levels of L-arganine may lead to reduced levels of bioavailabe NO, contributing to endothelial dysfunction.
How do N-3 polyunsaturated fatty acids (PUFAs) affect endothelial functioning (6)?
1: incorporation into cellular phospholipids -> reduction n-6 PUFAs -> a-infl. eicosanoids
2: reduction pro-inflammatory cytokines
3: increased NO synthesis\
4: reduced expression of endothelial adhesion molecules
5: improved VSMC sensitivity to NO
6: suppression of thromboxane A2
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