Lecture 12 Flashcards
Where are Vascular Smooth Muscle cells present?
in the tunica media of (some) blood vessels
What is the contractile unit for VSM? (2)
overlapping myosin actin filaments thin filaments (actin) are longer than myosin and therefore enable greater shortening
What does VSM rely on to initiate contraction?
Poorly developed SR so relies primarily on diffusion of Ca ions from ECF
What are actin filaments anchored to
cytoplasm?
cell membrane?
dense bodies in cytoplase
dense bands in cell membrane
what are the 2 broad groups of excitation-contraction coupling?
- Electromechanical coupling: depolarization of the VSM cell-> opening of L-type voltage gated Ca channels
- Pharmacomechanical coupling: binding of signaling molecule to a receptor leads to an inc of intracellular Ca [ ] ; either via G protein coupled release of intracellular stores or opening of receptor operated Ca channels (no change in membrane potential
VSM contraction steps (6)
Increase in intracellular Ca [ ] Ca + cadmodulin complex [Ca-cadmodulin] myosin light chain kinase Phosphorylation of MLCK myosin forms a crossbridge with actin contraction of VSM
What is different about VSM (5)
contracts slowly low energy requirements poorly developed SR cell-cell conduction via gap junctions no troponin, no voltage operated Na channels
inc tone of VSM (relative to basal tone)=
dec tone=
vasoconstriction
vasodilation
What maintains arterial BP?
basal vascular tone produced by VSM contraction sustained continually
Factors controlling vascular tone intrinsic mechanisms (3)
responsible for (2)
(entirely within the vasculature)
myogenic response
vasoactive metabolites
endothelial secretions
autoregulation, active and reactive hyperemia
Factors controlling vascular tone Extrinsic mechanisms (2)
Extrinsic can…
(factors outside the vasculature) Neural control (vasomotor nerves) hormonal control (vasoactive hormones)
extrinsic can override intrinsic to meet needs of the whole animal (ex. hemorrhage)
Myogenic response (intrinsic) depolarization is initiated by... Response is maintained by...
VSM contracts in response to stretch and relaxes with reduction in tension
stretch activated channels
tension sensitive channels
Vasoactive metabolites (intrinsic) function to... contribute to...
Metabolic products released into interstitial fluid cause alterations in local blood flow
- match bloodflow to metabolic demands of tissue
- active and reactive hyperemia
Metabolic (active) hyperemia
inc blood flow in response to increase metabolic rate (demand)
Reactive hyperemia
leads to…
peak flow and duration of hyperemia is
temporary inc blood flow following a period of reduced blood flow
rapid restoration of O2 supply and ‘wash out’ of accumulated waste products
directly proportional to duration of occlusion
Endothelial secretions (intrinsic) Vasodilation- Vasoconstriction-
produce a range of vasoactive molecules
- NO and Prostacyclin
- endothelin
endothelium induced flow dependent relaxation
-inc flow-> inc shear stress->ECs produce NO
NO induced endothelium dependent muscle relaxation
NO induced vasodilation
NO produced by…
NO signalling…
endothelial cells produce NO
- Activates Guanylyl cyclase (GC)
- GC converts GTP to cGMP
- cGMP activates kinases that promote relaxation
Autoregulation-
achieved by-
protects…
vascular resistance changes that tend to maintain a constant blood flow
-Myogenic response and flow induced endothelial relaxation
capillaries from exccessive hydrostatic pressure
Neural control(extrinsic) 2 types of autonomic nerves
Sympathetic nerves- predominately vasoconstrictive
parasympathetic nerves-vasodilator
but also-reduction in vasoconstriction-> vasodilation
Sympathetic Vasoconstrictor nerves
how do they work
fibers release vesicles containing NA
NA activates alpha1,2 adrenoreceptors causing vasoconstriction(arterioles of all organs and veins in the abdominal organs)
Sympathetic nerves
inc sympathetic activity->(3)
inc peripheral resistance (TPR)
dec local blood flow
displacement of blood from peripheral to central veins (inc venous return)
Alpha adrenoreceptor mediated constriction of smooth muscle (3)
G protein activates phospholipase C
cleaves membrane phospholipid to produce IP3
IP3 opens Ca channels on the SR
Parasympathetic nerves
how it works (2)
where it works(3)
-parasympathetic fibers release vesicles containing Ach
-Ach activates M3 muscarinic receptors on ECs->synthesis of NO->dilation
-coronary artery
-genital arterioles
salivary gland arterioles
Hormonal control (extrinsic)
Adrenaline/NA
-Beta 2 receptor-
-alpha 1 and 2 receptor
- vessel dilates(coronary circulation and skeletal muscle)
- vessel constricts (predominated in most tissues
Unlike alpha adrenoreceptors, Beta2 receptors are…
not innervated by sympathetic nerves->they respond to circulating Adr/NA
