Blood vessel order, function & specialisation of cells in the cardiovascular system Flashcards
What are the three layers of blood vessels?
Tunica intima -
Contains elastic basal lamina
in contact with the endothelium: this is the exchnage surface
Tunica media - mainly smooth muscle which is able to contract or dilate depending on the type of stimulus
Tunica adventitia - external layer containing blood vessels, collagen, elastin and fibrous tissue. This helps keep the shape of the blood vessel.
What is the vascular endothelium and what are the functions of the vascular endothelium?
Single cell layer of cells that acts as the blood-vessel interface.
1.Barrier
Prevents atheroma development & impedes pathogens
2.Growth
Mediates cell proliferation
3.Absorption + Secretion
Allows active/passive transport via diffusion/channels
4.
Thrombostasis
Prevents clots forming or molecules adhering to vessel wall
5.Vascular tone management
Secretes and metabolises vasoactive substances
How do blood vessels regulate its own blood pressure?
Blood vessels regulate their own pressure depending on how much blood is flowing past it (SHEAR STRESS).
Mechanoreceptors on the endothelial cells detect an increased blood flow and secrete vasodilators to bring the blood flow down.
What are the two main vasodilatory molecules? What other effect do they have?
Nitric Oxide: Inhibit aggregation of platelets
Prostacyclin (PGI2): Cardioprotective molecule. Anti-atherogenic
Anti-platelet
What are the three main vasoconstricting molecules?
Thromboxane A2: produced in endothelial cells but also by platelets.
Vasoconstrictor
Pro-atherogenic
Pro-platelet
Endothelin-1
Angiotensin II
What is vascular tone controlled by
it is controlled by the balance of the forces causing vasoconstriction and vasodilation
What is special about endothelin-1?
Endothelin-1 can cause BOTH vasoconstriction AND vasodilation - it has different receptors on different tissues
How is NO produced in the vascular endothelial cell and what are its effects?
- ACh binds to GPCR (G-protein-coupled receptors)
- PLC migrates along membrane
- PLC converts:
PIP2 —-> IP3 + DAG - IP3 triggers Ca2+ influx from ER
- Ca2+ upregulates eNOS (cytoplasmic enzyme = endothelial Nitric Oxide Synthase)
- eNOS converts L-Arg + O2 to L-Cit + NO
- NO diffuses into VSMC and activates GC (guanylyl cyclase)
- GC converts GTP to cGMP
- cGMP upregulates PKG
- PKG activates potassium channels
- Membrane hyperpolarises (negative)
- Cell relaxes
- Vessel dilates
What role does the EFFLUX of calcium play
Calcium efflux reduces tension within the myocyte and stimulates relaxation.
What role does acetylcholine play in blood vessels?
What is the role of phosphodiesterase enzyme in the action of NO?
Acetylcholine UPREGULATES activation of endothelial nitric oxide
This leads to steady vasodilation.
Phosphodiesterase enzyme starts to breakdown cGMP to GMP
Give an example of a nitric oxide donor.
SNP - sodium nitroprusside
Describe how thromboxane A2 and prostacyclin is made
- Phospholipid —————> Arachidonic Acid
Enzyme: Phospholipase A2 - Arachidonic acid ————-> Prostaglandin H2
Enzyme: COX1 ~(cyclooxygenase) + COX2 . - Prostaglandin H2 can then be converted to:
Thromboxane A2 (by Thromboxane Synthase) OR
Prostacyclin (by Prostacyclin Synthase), or PGD2, PGE2, PGF2
which cyclooxygenase is produced more in response to inflammation?
Cyclooxygenase 2 will be upregulated if your body has an inflammatory problem.
Describe how leukotrienes are produced from arachidonic acid.
Lipoxygenase enzymes convert arachidonic acid to: LTA4, LTB4, LTC4 and LTD4
What are the leukotrienes that are produced by the lipoxygenase enzymes and what effect does LTD4 have?
LTA4, LTB4, LTC4 and LTD4
LTD4 causes BRONCHOCONSTRICTION and LTD4 is associated with asthma, therefore bronchoconstriction
What therapy blocks the action of LTD4?
Montelukast Therapy which reduces broncoconstriction helping the patient breathe more comfortably.
how does thromboxane and prostacyclin work?
Prostacyclin
Vasodilator
Anti-atherogenic
Anti-platelet
Thromboxane A2
Vasoconstrictor
Pro-atherogenic
Pro-platelet
This is why thromboxane is typically bad for the cardiovascular system and prostacylin has cardio-protective properties.
What enzyme produces arachidonic acid from DAG?
DAG (diacylglycerol) lipase converts DAG to Arachidonic acid
How is prostacyclin produced and what are its effects?
- PGI2 (prostacyclin) produced via COX1 (and COX2) = cyclooxygenase
- PGI2 diffuses into VSMC
- PGI2 binds to IP (prostacyclin) receptor
- Upregulation of adenylyl cyclase (AC)
- AC converts ATP to cAMP
- cAMP inhibits MLCK
- Reduced cross-bridge cycling
- Cell relaxes
- Vessel Dilates
what effect does prostacyclin have when it is secreted in the blood
it has anti-platelet aggregation properties
Where is thromboxane produced?
Where is thromboxane synthase enzyme mainly found?
- Endothelial Cells
- Platelets
Platelets
What are the two types of receptor for thromboxane and where are they found?
Alpha = Platelets Beta = Smooth Muscle Cell
Describe the mechanism of action of thromboxane on vascular smooth muscle cells.
what happens when thromboxane binds to platelets
Thromboxane binds to Beta receptor on smooth muscle cell and activates PLC
- TXA2 (thromboxane) diffuses through apical and basement membrane
- TXA2 binds to TPβ on VSMC
- PLC migrates along membrane
- PLC converts PIP2 to IP3+DAG
- IP3 triggers Ca2+ influx from extracellular space and SER
- Ca2+ upregulates MLCK
- VSMC contracts
- Vessel constricts
- TXA2 binds to TPα on platelets
- Platelet becomes ‘active’ and produces more TXA2
- Positive feedback potentiates response
- Platelets aggregate
What effect does endothelin-1 have on smooth muscle cells?
CONSTRICTION