Lecture 12: Vascular Smooth Muscle Function Flashcards
describe the cell shape and features of a vascular smooth muscle cells
- spindle shaped
- overlapping actin and myosin contractile unit
- thin filament longer
- poorly developed SR (rely primarily on diffusion of Ca2+ ion from ECF to initiate contraction)
- no striations, appear wrinkled
- actin filament anchored to dense body instead of Z band in cytoplasm
how is vascular smooth muscle contraction triggered?
contraction triggered by a rise in intracellular calcium
most of the intracellular calcium arises from influx of extracellular calcium
what are the 2 broad groups of excitation-contraction coupling? (how we get an increase in intracellular calcium)
- electromechanical coupling - depol of the vsm cell = opening of L type voltage gated calcium channels
- pharmacomechanical coupling - binding of signalling molecule to a receptor leads to increase in intracellular calcium via g protein or receptor operated calcium channel
describe the vascular smooth muscle contraction
- increase in intracellular calcium caused by electromechanical or pharmacomechanical
- calcium and calmodulin form a complex
- calcium and calmodulin complex with myosin to form myosin light chain kinase
- myosin LCK phosphorylised
- myosin forms a cross bridge with actin
- contraction of SMC
- no troponin in SMC must form complex with calmodium
what is different about vascular smooth muscle?
- contracts slowly, maintains tone
- low energy requirements
- poorly developed SR
- cell to cell conduction with gap junctions
- no troponin, no VO Na channels
what is vascular tone
the state of contractile tension in vessel walls
basal level not fully relaxed
vasal tone produced by vascular contraction and maintained throughout animals life - maintaining MAP
what are the factors controlling vascular tone?
- intrinsic mechanisms; entirely within the vasculature myogenic response, vasoactive, endothelial secretions responsible for auto regulation and active/ reactive hyperaemia
- extrinsic mechanisms: outside the vasculature: neural control, hormonal control
what is the myogenic response
intrinsic mechanism
VSM contracts in response to stretch and relaxes with reduction in tension
important because - contributes to basal tone, stabilises tissue blood flow if arterial pressure changes
where is the myogenic response particularly prominent?
cerebral and renal arteries - where we need constant oxygen
how is the myogenic response initiated and sustained?
mediated by depol and Ca2+, depol initiated by stretch-activated channels and sustained by TENSION sensitive channels
what re vasoactive metabolites
metabolic products released into interstitial fluid causing alterations in local blood flow
what is the function of vasoactive metabolites?
to match blood flow to metabolic demands of the tissue
eg/ increase metabolic work - increase oxygen demand - increase release of vasodilators and brings in more blood
what is metabolic hyperaemia
increase blood flow in response to an increase in metabolic rate (O2 demand)
what is reactive hyperaemia
temporary increase in blood flow following a period of reduced blood flow.
leads to rapid restoration of oxygen supply and wash out of accumulated waste products, restoring potentially hypoxic tissue
how is the duration of the reactive hyperaemia variable?
peak flow and duration of hyperaemia is proportional to duration of occlusion
what is a major function of endothelial cells
regulation of vascular smooth muscle tone
what is endothelial induced flow dependent relaxation
with increased flow and sheer stress of endothelial cells, the EC’s produce NO
what is NO signalling
sheer stress stimulates NO synthase to produce NO via L-arginine
NO diffuses to SMC and activates gunnel cyclase
GC converses GTP to cGMP
cGMP activates kinases that promote relaxation
what is autoregulation
the maintenance of constant blood flow even in the face of vascular resistance
preserves tissue flow and protects capillaries from excessive hydrostatic pressure
achieved by: myogenic response and endothelial cell flow induced relaxation
where does the myogenic response predominate?
in resistance vessels
where does the metabolic vasodilators predominate?
in most metabolically active tissues e.g. capillaries
what are the two major nerves involved with extrinsic neural control
sympathetic nerves - predom vasoconstrictor
parasymp nerves - predom vasodilator
what do the sympathetic fibres release and how does it act?
symp fibres release NA
NA activates a-adrenoreceptors causing vasoconstriction
symp activity = increase TPR
decrease blood flow –> displacement of blood from periphery to central
describe the action of NA on smooth muscle contraction
NA –> a-adrenoreceptor (g protein coupled) –> activates phospholipase C –> cleaves memb phospholipid –> IP3
IP3 opens channels in the SR
= DIRECT action on smooth muscle cell
what do the parasympathetic fibres release and how does it act?
parasymp fibre release ACh
ACh activates M3 receptor on EC –> synth NO –> dilation
= INDIRECT action on SMC
describe how hormonal control contributes to basal tone
adrenaline
from adrenal medulla
a1 and a1 = predom most tissues cause contrstriction
b1 = heart dilation
b2 = vessel dialtion
b2 innervated ONLY by circulating levels of adrenalin, not by symp fibres.
e.g. of how extrinsic control can override intrinsic control
HAEMORRHAGE
- blood vessel not ligated properly = blood pooling, tissue start becoming hypoxic, decreased CBF
- blood pooling increases metabolites
- intrinsic system wants to dilate (would make problem worse)
- extrinsic overrides and begins sympathetic stim
- increase TPR, decrease local blood flow and vasoconstriction = displacement of blood
- partial restoration fo cardiac filling
