Physiology and Pharmacology 15: (Evans) Sympathetic control of arteries

Question 1

Main distinction of the terminal of a sympathetic nerve?

Answer 1

Noradrenaline Varicosities present -> release sites for NA

Question 2

Receptors which bind NA and result in vasoconstriction? Pathway?

Answer 2

a1-adrenoceptors -> Gq coupled IP3 pathway

Question 3

Name 3 sites of action to block artery contraction - example of drug for each

Answer 3

Block

• NA release (Reserpine)
• adrenoceptor antagonists (
• effects on calcium

Question 4

How is Noradrenaline usually recycled and re-stored from the synaptic cleft? How does reserpine affect this?

Answer 4

Noradrenaline taken back into sympathetic varicosities via uptake1 protein
- pumped back into vesicles via NA pumps

Reserpine recognised and uptaken by uptake1 -> then binds to NA pump and blocks action -> reduction in NA available for release

Question 5

Describe function of agonists and antagonists for alpha1 adrenoceptors - example?

Answer 5

Agonists - treatment of hypotension and shock
- e.g. methoxamine and phenyeprine lead to an increase in BP through a1-adrenoceptor activation on smooth muscle

Antagonist - treatment of hypertension (high BP)
- e.g. prazosin, blocks NA induced artery constriction

Question 6

Describe function of agonists and antagonists for alpha2 adrenoceptors - example?

Answer 6

Agonists - act presynaptically to inhibit transmitter release (prejunctional receptors)

e.g. clonidine, methylDOPA

Antagonists - block prejunctional a2-receptors -> results in increases NA release
- HOWEVER Some systems a2r are postjunctional so may have complex effects

Question 7

Describe mechanisms of calcium in artery contraction - methods of calcium release

Answer 7

Calcium + calmodulin -> calcium-calmondulin
Upon +ve stimulation -> binds to MLCK -> phosphorylates myosin -> contraction

1) sympathetic nerve stimulation -> depolarisation of smooth muscle -> activates Voltage dependant Ca channels
2) a-adrenoceptor activation couples through Gq proteins and IP3 pathway -> calcium store release

Question 8

3 types of voltage dependent calcium channels?

Answer 8

N-type: on Neurons involved with transmitter release

T-type: in brain and heart, Transient opening

L-type: on smooth muscle, Long lasting

Question 9

Which type of Ca channel would an anti hypertensive antagonist target?

Answer 9

L-type channels -> block
e.g. dihydropyradines (DHPs) acting on smooth muscle
, other drugs which block channel pores

Question 10

What are the 3 modes of calcium channels? Mode of action of DHPs?

Answer 10

3 modes

• mode 0: <1%, cannot normally open on depolarisation
• mode 1: ~70%, low probability of opening on dp.
• mode2: ~30%, high probability of opening on dp.

DHPs bind to channels and stabilise different modes (dont block pores)

• can stabilise mode 0 (e.g. nifedipine)
• can stabilise mode 2 (e.g. BAY K 8644)