Vascular endothelium Flashcards Preview

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Flashcards in Vascular endothelium Deck (21)
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1
Q

What are the functions of endothelial cells?

A
  • permeability
  • synthesize collagen and proteoglycans
  • synthesize and secrete molecules which promote protective thrombus formation ( like Factor 8)
  • synthesize and secrete molecules with minimise pathological thrombus formation ( nitrous oxide )
  • secrete vasoactive factors controlling blood flow
  • produce molecules which mediate the acute inflammatory reaction (interleukins 1,6,8 etc)
  • produce some growth factors- fibroblast growth factor etc.
2
Q

In particular what is the role of the endothelium on hemostasis?

A
  • Secretes NO, PGI2 to inhibit platelet activation
  • Prevents exposure of platelets to sub-endothelial matrix components such as collagen
  • Produces heparin to inhibit the coagulation cascade (heparin is expressed on endothelial cell surface)
  • Produce thrombomodulin which, when bound to thrombin, can generate activated protein C which degrades FVa and FVIIIa. (expressed on endothelial cell surface)
  • Secretes tPA and urokinase to degrade formed clots. (secreted into plasma in vicinity of intact endothelium)
3
Q

nitric oxide is a what?

endothelin is what?

A

nitric oxide = vasodilator

endothelin A = vasconstrictor

Endothelin B = vasodilator

4
Q

What are prostacyclins?

A

they are vasodilators

  • is a product of arachidonic acid produced by cyclooxygenase
  • inhibits platelet aggregation and promotes blood vessel dilation
  • it’s counterpart is thromboxane 2 which is produced by platelets and promotes platelet aggregation and cuases blood vessel constriction in hemostasis
5
Q

what is endothelium derived relaxing factor?

A

it is a NO free radical and is therefore unstable with a very short half life - it can be produced enzymatically or chemically -

it is a potent vasodilator -used in the treatment of angina as it helps with ischemic pain by decreasing the cardiac workload - it is also an air pollutant produced by cigarette smoke, automobiles and power plants -

6
Q

What is ‘good nitric oxide synthase’?

A

eNOS or NOS 3= found in endothelial cells

7
Q

What is ‘bad’ Nitric oxide synthase?

A

iNOS or inducible nos= inducible in many tissues and innapropriately oxidizes things like LDLs

8
Q

what are the physiological effects of nitric oxide/cyclic GMP?

A
  • Vascular effects include vasodilation & inhibition of platelet aggregation
  • Immunological effects include inhibition of neutrophils & monocytes
  • In blood vessels, cGMP causes relaxation of vascular smooth muscles lead to vasodilation and increased blood flow.
9
Q

the actions of nitric oxide and cyclic GMP are terminated by what enzyme?

A

phosphodiesterases - regulate the localization, duration, and amplitude of cyclic nucleotide signalling

* they are very localized enzymes which makes them great drug targets*

10
Q

what kind of drugs are PDE 5 inhibitors?

A

Sildenafil= viagra

Tadalfil

Vardenafil

11
Q

what is the difference between an on-target and off-target side effect?

A

on target= on the right ezyme, but producing the wrong effect

off target = on the wrong enzyme and causing the wrong effect

12
Q

what are nitric oxide synthase inhibitors used for?

A

•Inhibitors of NOS, while widely used in experimental research, are still in under investigation for clinical applications

13
Q

What are endothelins?

A

•Endothelin is a family of 21 amino acid peptides

–ET-1 is found in endothelial cells, brain and kidney

–ET-2 is found in the kidney and intestines

–ET-3 is found in the brain, lung, intestines and adrenal glands

  • endothelins are the strongest vasoconstrictors known
  • There are three isoforms with varying regions of expression and two key receptor types, ETA and ETB.
14
Q

What is the synthesis of endothelin inhibited by?

A

by NO and prostacyclin

15
Q

What are the two types of endothelin receptors?

A

•ETA

–ETA receptors stimulate phospholipase C

–ETA receptors are found in the smooth muscle tissue of blood vessels

–binding of endothelin to ETA increases vasoconstriction and the retention of sodium ->increased blood pressure.

•ETB

–ETB: Activate phospholipase C

–ETB receptors located on the endothelial cells

–ETB receptors linked to increased natriuresis and diuresis and the release of nitric oxide (NO), all mechanisms that lower the blood pressure.

16
Q

What drug is an ETA/B receptor antagonist?

A

–Bosantin is an ETA/B receptor antagonist

–used in the treatment of Pulmonary Hypertension

17
Q

Name a drug that is an ETA selective antagonist

A

–Ambrisentan and Sitaxsentan are ETA selective antagonist

–ETA selective antagonists decrease the vasoconstrictive actions and allow an increased beneficial effects of endothelin B stimulation, such as nitric oxide production

18
Q

All endothelin drugs can have what side effect?

A

–All endothelin antagonist drugs can induce liver damage and need to be monitored closely

19
Q

What is the effect of endothelium derived hyperpolarizing factors?

A
  • Induces relaxation of smooth muscle due to hyperpolarization
  • Diffuse from the endothelium
  • Is not NO or prostacyclin
  • Activated by Ga subunit
  • Unlikely to be CO
  • EDHFs have a short half life
20
Q

what vasoactive agents are released by the endothelium to regulate vascular tone?

A

–NO (vasodilator)

–Prostacyclin (vasodilator)

–EDRF (vasodilator; = NO)

–Endothelin (vasoconstrictor)

–EDHF (vasodilator)

•In a healthy individual, a delicate balance between vasoconstriction and vasodilation is maintained by endothelin, calcitonin and other vasoconstrictors on the one hand, and nitric oxide, prostacyclin and other vasodilators on the other.

21
Q

when do we use prostacyclin?

A

used intravenously - as a vasodilator in sever Raynaud’s phenomenon or ischemia of a limb -