Blood vessel order, function & specialisation of cells in the cardiovascular system Flashcards Preview

LSS 1 - CVS - Laz > Blood vessel order, function & specialisation of cells in the cardiovascular system > Flashcards

Flashcards in Blood vessel order, function & specialisation of cells in the cardiovascular system Deck (33)
1

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

2

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.

3

What are the two main vasodilatory molecules? What other effect do they have?

Nitric Oxide
Prostacyclin
Inhibit the aggregation of platelets

4


What are the three main vasoconstricting molecules?

Thromboxane A2
Endothelin-1
Angiotensin II

5

What is special about endothelin-1?


Endothelin-1 can cause BOTH vasoconstriction AND vasodilation - it has different receptors on different tissues

6

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

7


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

8

What role does acetylcholine play in blood vessels?

Acetylcholine UPREGULATES eNOS
This leads to steady vasodilation

9

Give an example of a nitric oxide donor.

SNP - sodium nitroprusside

10


Describe how arachidonic acid is produced.


Phospholipid ---------------> Arachidonic Acid
Enzyme: Phospholipase A2

11

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)

12

Describe how leukotrienes are produced from arachidonic acid.


Lipoxygenase enzymes convert arachidonic acid to: LTA4, LTB4, LTC4 and LTD4

13

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

14

What therapy blocks the action of LTD4?

Montelukast Therapy

15

What enzyme produces arachidonic acid from DAG?

DAG lipase

16

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

17


Where is thromboxane produced?

Endothelial Cells
Platelets

18

What are the two types of receptor for thromboxane and where are they found?


Alpha = Platelets
Beta = Smooth Muscle Cell

19

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+
VASONCONSTRICTION

20

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)

21

What effect does endothelin-1 have on smooth muscle cells?

CONSTRICTION

22

What two types of receptors does endothelin-1 have?

Alpha and Beta receptors

23

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

24

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)

25

What effects do angiotensin II have?

Increase Vascular Resistance:
Vasoconstriction
Increase sympathetic activity
Increase Water Retention:
Increase sodium reabsorption
Increase vasopressin secretion
Increase aldosterone production

26

What other action does ACE have other than converting angiotensin I to angiotensin II?

It breaks down bradykinin

27

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

28

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)

29

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

30

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.

31

What is the effect of low dose aspirin on prostacyclin and thromboxane production?

Maintains high prostacyclin production while decreasing thromboxane production

32

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.

33

What is the problem with designing calcium channel blockers and what is the solution?

A calcium channel blocker needs to be designed such that it doesn't interfere with the calcium channels in the heart.
Solution: the affinity of the calcium blocker to the channel is dependent on MEMBRANE POTENTIAL
Smooth muscle cells have a MORE POSITIVE membrane potential than cardiomyocytes