Lecture 5: Vascular Biology Flashcards
Where is flow fastest? Slowest?
In the middle of the vessel
Along the endothelium
What is the difference between laminar and turbulent flow?
Laminar is all in one direction
Turbulent can go in different direction pg. 5 of ppt
What is shear stress? Significance?
Friction between layers of fluids sliding over each other
These forces affect endothelial function
Endothelial cell can change its morphology based on sheer stress
What is rheology?
The study of the flow of matter, primarily in the liquid state
What is an example of hyperemia?
Dilation of the artery that lasts for 10 minutes AFTER application of a blood pressure cuff
What are conduit arteries?
The highways (aorta) Carries shit directly from one place to another
What are the 4 roles of the endothelium?
- Modulates TONE
- Modulates GROWTH
- Modulates HEMOSTASIS
- Modulates INFLAMMATION
Endothelium is the business end of the CV system
How does endothelium vasodilate?
- NO (aka endothelial derived relaxing factor or EDRF)
- Prostacyclin (PG12)
- Bradykinin
- Acetylcholine
Therefore you need an INTACT endothelium to vasodilate
What is endothelial derived relaxing factor?
Nitric oxide
True or false, an intact endothelium is necessary for vasodilation?
True
How is NO synthesized?
Synthesized from L-arginine by NO synthase (eNOS or NOS III from endothelial cell)
Enzyme is stimulated by blood flow across the endothelial cell surface (shear stress) or by chemical mediators like Ach
What is the MoA of NO?
NO diffuses to underlying smooth muscle cells
NO stimulates GUANYLATE CYCLASE and generates cGMP
cGMP will cause SMC to relax
Substance P, bradykinin, ACh and B-agonists regulate NO
What are the two roles of Ach? What accounts for this pseudoparadox?
Ach can vasodilate AND vasoconstrict
Ach can vasodilate by interacting with the Ca-calmodulin pathway within the ENDOTHELIAL cell to promote NO synthesis
ACh can vasoconstrict by acting DIRECTLY on the smooth muscle cell
Significance of roles of Ach in vasoconstriction/dilation?
If arteries vasodilate, endothelial cells intact
If arteries vasoconstrict, endothelial cells are damaged so NO diffuses directly to smooth muscle cells
So if coronary vessels vasoconstrict with ACh, then you know that there is atherosclerotic damage
What are the key features of NO?
A gas released by endothelium
Release stimulated by
i. shear stress
ii. physiologic agonists
iii. pathologic insults
Inhibits platelet activation, secretion and aggregation; maintains vascular relaxation
Low levels of NO maintain vessel in state of dilation in normal state