Flashcards in Blood vessel order, function & specialisation of cells in the cardiovascular system Deck (33)
What are the three layers of blood vessels?
Tunica intima - mainly vascular endothelium
Tunica media - mainly smooth muscle
Tunica adventitia - external layer containing blood vessels, collagen, elastin
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?
Inhibit the aggregation of platelets
What are the three main vasoconstricting molecules?
What is special about endothelin-1?
Endothelin-1 can cause BOTH vasoconstriction AND vasodilation - it has different receptors on different tissues
Describe the synthesis of nitric oxide.
A substrate that triggers NO production will bind to a Gq protein linked receptor and activate PLC.
PIP2 ----> IP3 + DAG
IP3 ----> increase intracellular [Ca2+] (release from SR)
Increased [Ca2+] ---> activate endothelial nitric oxide synthase
Nitric Oxide Synthase catalyses:
L-arginine + Oxygen ---> L-citrulline + NO
Describe the action of nitric oxide.
Nitric Oxide binds to receptors on smooth muscle cells and activates GUANYLYL CYCLASE ---> increase in cGMP ---> activation of Protein Kinase G ---> RELAXATION
What role does acetylcholine play in blood vessels?
Acetylcholine UPREGULATES eNOS
This leads to steady vasodilation
Give an example of a nitric oxide donor.
SNP - sodium nitroprusside
Describe how arachidonic acid is produced.
Phospholipid ---------------> Arachidonic Acid
Enzyme: Phospholipase A2
Describe how prostaglandins are produced from arachidonic acid.
Arachidonic acid -------------> Prostaglandin H2
Enzyme: COX1 + COX2
Prostaglandin H2 can then be converted to:
Thromboxane (by Thromboxane Synthase)
Prostacyclin (by Prostacyclin Synthase)
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
What therapy blocks the action of LTD4?
What enzyme produces arachidonic acid from DAG?
Describe the mechanism of action of prostacyclin.
Prostacyclin binds to a receptor on smooth muscle cells and activates ADENYLATE CYCLASE ---> increase in cAMP ---> activate PKA ---> relaxation
Where is thromboxane produced?
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.
Thromboxane binds to Beta receptor on smooth muscle cell and activates PLC
PIP2 ---> IP3 + DAG
Increase in Ca2+
What effect does endothelin-1 have on endothelial cells?
Endothelin-1 can bind to beta receptors on endothelial cells and cause ACTIVATION OF eNOS (leading to VASODILATION)
What effect does endothelin-1 have on smooth muscle cells?
What two types of receptors does endothelin-1 have?
Alpha and Beta receptors
What is the mechanism of action of endothelin-1 on vascular smooth muscle cells?
Alpha and Beta receptors on smooth muscle are linked to PLC.
Endothelin-1 can bind to either and the result is CONTRACTION
Describe the production of angiotensin II.
Renin is released by juxtaglomerular cells
Renin converts angiotensinogen (produced by the liver) to angiotensin I
Angiotensin I is converted to Angiotensin II by ACE (mostly found in the lung endothelium)
What effects do angiotensin II have?
Increase Vascular Resistance:
Increase sympathetic activity
Increase Water Retention:
Increase sodium reabsorption
Increase vasopressin secretion
Increase aldosterone production
What other action does ACE have other than converting angiotensin I to angiotensin II?
It breaks down bradykinin
What is the mechanism of action of bradykinin on endothelial cells and what effect does it have?
Bradykinin binds to its receptor on endothelial cells.
PLC: PIP2 ----> IP3 + DAG
Results in UPREGULATIONG OF eNOS -----> increase in NO -----> VASODILATION
How do we go about increasing the diameter of blood vessels?
Increase NO by:
Stimulate the production of NO
Give an NO donor (e.g. SNP)
Describe the mechanism of action of viagra.
NO works by activating guanylyl cyclase, which then converts GTP ---> cGMP
The increase in cGMP causes relaxation (vasodilation)
cGMP is eventually broken down by PHOSPHODIESTERASE to GMP
Viagra is a PHOSPHODIESTERASE INHIBITOR
How does aspirin affect the synthesis of prostaglandins?
Aspirin causes irreversible inhibition of COX enzyme
This reduces the conversion of arachidonic acid to prostaglandin H2 and hence decreases production of prostaglandins.
What is the effect of low dose aspirin on prostacyclin and thromboxane production?
Maintains high prostacyclin production while decreasing thromboxane production
Why does low dose aspirin have this effect?
Thromboxane is mainly produced by platelets, which have NO NUCLEUS
So the platelets can't produce more COX. Aspirin irreversibly binds to the COX in the platelets and the platelets can't make more COX to compensate.
Endothelial cells can make more COX so their prostacyclin levels remains high.