Flashcards in Smooth Muscle Deck (34):
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
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+
Small, thick-walled vessels -> vascular resistance ->
Oedema is caused from
Increased capillary hydrostatic pressure / increased capillary permeability
Highly distensible + large fraction blood volume
Systematic venules/veins ->
Volume reservoir approx. 5%
1. Mech -> myogenic response -> passive
2. Elec. -> opening L-type Ca channels
How does NA bind to VSM?
From sympathetic nerves via a1-adrenoreceptors coupled via Gq to PLC + InsP3 production
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
Alpha 1- adrenoreceptor antagonists act as
Vasodilators e.g. prazosin, indoramine -> cause vasodilation + fall in bp
Amphetamine, tyramine and ephendrine mech. of action
Indirect acting vasoconstrictors that cause NA release from nerve terminals
Sympathomimetic effect -> Blocks uptake of NA into nerve terminals
How is Angiotensin II produced?
ATI -> ATII by ACE in vascular endothelial cells
Example of ACE inhibitor
How does AII lead to VSM contraction
acts via AI receptors coupled via Gq to PLC + Insp3 production
Endothelin (ETA and ETB2) characteristics
21 aa peptides, 3 isoforms
How does ET1 lead to VSM contraction
ET1 acts via ETA and ETB2 receptors coupled to Gq
BQ-123, BMS 182874
Vasporessin is a
Posterior pituitary hormone with major actions on kidney
Vascular actions of VP
Via V1 receptors to elicit VSM contraction + constriction of GI and uterine SM
What is the name of a VP analog and how is it used?
Felypressin -> vasoconstrictor with LA's
How does ergotamine work to reduce migraine?
Migraine = dilation of cerebral blood vessels
-> ergotamine -> marked vasoconstriction
How does sumatriptan act to reduce migraine?
5-HT1D like receptor agonist -> constricts intracranial vascular smooth muscle - possibly trigeminal muscles
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.
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.
2. NO -> respiratory disease syndrome
3. Drugs that act via receptors on endothelium to stimulate NO synthase
4. NO inhibitor for septic shock
How does viagra work?
Pelvic stimulation -> NO release -> relax sm of corpus cavernosum -> NO metabolised by PDE-5
Sildenafril (viagra) inhibits PDE-5
Calcium antagonist -> block calcium channel -> fall bp + reflex tachycardia
Muscarinic receptor antagonist -> used as an anti-asthmatic drug + given by aerosol inhalation
- quaternary compound so low lipid solubility
- can't cross BBB
Methyl xanthine bronchodilator q
- slow IV infusion to induce labour -> regular contractions
- higher doses: reduce postpartum haemorrhage
Ergometrine use in uterine SM
Evokes contraction of sm used with oxytocin to contract uterus
Therapeutic abortion drugs
Prostaglandins E2 and F2a -> marked rythmical contractions