Lecture 5 - Vascular Pharmacology

Question 1

Name the two pathways for contraction

Answer 1

Agonist mediated pathway
Electromechanical coupling

Question 2

Name the endothelial derived vasodilators

Answer 2

Nitric oxide or EDRF (endothelial-derived relaxing factor)
Prostaglandins - PGI2 or prostacyclin (others PGE2, PGD2)
Endothelium-derived hyperpolarising (EDH) factors

Question 3

Describe the nitric oxide synthase isoforms

Answer 3

Neuronal NOS - calcium-dependent
- CNS - neurotransmission, LTP, plasticity
- Peripheral NS - gastric emptying, penile erection
Inducible NOS - calcium-independent
- Macrophages, neutrophiles, leukocytes
Endothelial NOS - constitutively expressed - calcium-dependent
- Effect on blood vessels via NO - vasodilation
- Effects on platelets via NO - reduced platelet adhesion/ aggregation

Question 4

What is eNOS activated by?

Answer 4

Agonists
- Acetylcholine
- Bradykinin
- Histamine
- Endothelin-1
Shear stress
Insulin

Question 5

Describe the MoA of endothelial NOS in the endothelial cell

Answer 5

Activated by increases in cytosolic Ca2+ and or phospohorlation
Synthetises NO from L-arguinine and oxygen
NO diffuses out of the endothelial cell

Question 6

Describe the MoA of NO in smooth muscle cell

Answer 6

Activates soluble guanylyl cyclase (sGC)
sGC converts GTP-cGMP
cGMP directly stimulates MLCP and via activation of protein kinase G (PKG)
cGMP is broken down by PDE5

Question 7

Name a drug targeting eNOS and NO signalling pathway

Answer 7

Asymmetric dimethylarginine (ADMA)

Question 8

Name competitive NOS inhibitors (experimental)

Answer 8

Nitroarginine
L-NAME

Question 9

Name NO donors

Answer 9

Glyceryl trinitrate (GTN)
Sodium nitroprusside (SNP)

Question 10

Name some experimental NO donors

Answer 10

SNAP
SNOG

Question 11

Name a PDE5 selective inhibitor

Answer 11

Prevent cAMP breakdown
Sildenafil

Question 12

Name two cycle-oxygenases

Answer 12

COX-1 (constitutive) and COX-2 (inducible)