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Flashcards in Smooth Muscle Deck (34):
1

Mech of smooth muscle contraction

1. Increase I.C. Ca2+
2. Ca 2+ binds calmodium
3. Ca-calmodium activates MLCK
4. Phosphorylates MLC's in presence of ATP
-> 20-kd reg, subunits in myosin head
5. Cross-bridge formation -> s.m. contracts

2

Ca2+ movement in blood vessels

1. Ca2+ enters cell from external environment
2. Ca2+ released by I.C. storage sites (SR) -> ATP-dep ca2+ pump
3. Removal -> ATP- dep. Ca2+ pump/ Na+/ Ca2+

3

Arterioles

Small, thick-walled vessels -> vascular resistance ->
"circulatory stopcocks"

4

Oedema is caused from

Increased capillary hydrostatic pressure / increased capillary permeability

5

Venules/ veins

Highly distensible + large fraction blood volume

6

Systematic venules/veins ->

Volume reservoir approx. 5%

7

VSM contraction

1. Mech -> myogenic response -> passive
2. Elec. -> opening L-type Ca channels
3. Chem.

8

How does NA bind to VSM?

From sympathetic nerves via a1-adrenoreceptors coupled via Gq to PLC + InsP3 production

9

Co-transmitters for NA

- ATP - can cause contraction via activation of non-selective cation channel e.g. P2X
- Gq coupled to PLC e.g. P2Y
- NPY mech of action not clear but potentiate action ofNA

10

Alpha 1- adrenoreceptor antagonists act as

Vasodilators e.g. prazosin, indoramine -> cause vasodilation + fall in bp

11

Amphetamine, tyramine and ephendrine mech. of action

Indirect acting vasoconstrictors that cause NA release from nerve terminals

12

Cocaine effect

Sympathomimetic effect -> Blocks uptake of NA into nerve terminals

13

How is Angiotensin II produced?

ATI -> ATII by ACE in vascular endothelial cells

14

Example of ACE inhibitor

Catopril

15

How does AII lead to VSM contraction

acts via AI receptors coupled via Gq to PLC + Insp3 production

16

Endothelin (ETA and ETB2) characteristics

21 aa peptides, 3 isoforms

17

How does ET1 lead to VSM contraction

ET1 acts via ETA and ETB2 receptors coupled to Gq

18

Endothelin antagonists

BQ-123, BMS 182874

19

Vasporessin is a

Posterior pituitary hormone with major actions on kidney

20

Vascular actions of VP

Via V1 receptors to elicit VSM contraction + constriction of GI and uterine SM

21

What is the name of a VP analog and how is it used?

Felypressin -> vasoconstrictor with LA's

22

How does ergotamine work to reduce migraine?

Migraine = dilation of cerebral blood vessels
-> ergotamine -> marked vasoconstriction

23

How does sumatriptan act to reduce migraine?

5-HT1D like receptor agonist -> constricts intracranial vascular smooth muscle - possibly trigeminal muscles

24

Mechanism of VSM relaxation

1. cAMP stimulation of PKA -> phosphorylates and opens KATP channels.
2. hyperpolarization of smooth muscle cells
and closing of voltage-gated Ca2+ channels.
3. decreases intracellular [Ca2+] and so MLC phosphorylation, thereby
4. decreasing the interactions between actin and myosin. 5. drugs which increase cAMP (e.g., 2-adrenoceptor agonists, phosphodiesterase inhibitors) cause vasodilation.

25

How does NO regulate VSM tone?

Through cGMP :
cGMP can activate a cGMP-dependent
protein kinase, inhibit calcium entry into the VSM, activate K+ channels, and decrease IP3.

26

NO drugs:

1. Nitrovasodilators
2. NO -> respiratory disease syndrome
3. Drugs that act via receptors on endothelium to stimulate NO synthase
4. NO inhibitor for septic shock

27

How does viagra work?

Pelvic stimulation -> NO release -> relax sm of corpus cavernosum -> NO metabolised by PDE-5
Sildenafril (viagra) inhibits PDE-5

28

Nifedipine

Calcium antagonist -> block calcium channel -> fall bp + reflex tachycardia

29

Ipratropium bromide

Muscarinic receptor antagonist -> used as an anti-asthmatic drug + given by aerosol inhalation
- quaternary compound so low lipid solubility
- can't cross BBB

30

Theoprylline (aminophylline)

Methyl xanthine bronchodilator q

31

Oxytocin

PPH hormone
- slow IV infusion to induce labour -> regular contractions
- higher doses: reduce postpartum haemorrhage

32

Ergometrine use in uterine SM

Evokes contraction of sm used with oxytocin to contract uterus

33

Therapeutic abortion drugs

Prostaglandins E2 and F2a -> marked rythmical contractions

34

Salbutamol

- SM relaxation -> beta 2 - adrenoreceptor antagonist
- premature labour -> relax uterine muscle