Regulation of Vascular Function Flashcards
Distribution of CO and change in exercise
Rest, about 5L/min,with 15% to brain, 20% to liver and kidneys
Exercise:80-85% goes to muscle and skin(thermoregulation), and CO rises 4-5 fold to 20-25 L/min
Blood vessel innervation and SM amount and what it does
Arteries and arterioles (pre-capillary resistance vessels)are most densely innervated by sympathetic nerve fibres. Also more SM here
SM contraction and dilation will alter extent of blood flow and resistance etc
Post capillary vessels smaller proportion of both
- Revise water movement in capillaries
- Pressure drops across vasculature
-Net fluid movement: k[(Pc-Pt)-(plasma colloid-tissue colloid)]
Net fluid movement out due to high HP on pre capillary side, fluid moves in on venous side, as HP lowers
- Aorta and large vessels small drop
- Pre capillary largest drop due to them being resistance vessels
- Small drop in capillaries, venules and veins
How does increasing and decreasing pre capillary resistance alter fluid movement in the capillary
what is it regulated by
Increased resistance: Decreased HP, leading to more fluid absorption
Decreased pre capillary resistance: More fluid extruded
sympathetic drive
Autoregulation demonstrated on perfusion blood flow graph, in absence of what?
Decrease PP: acute drop in BF, then corrects
Increase PP: acute increase then levels out
absence of neural/humoral output
What is reactive hyperaemia?
Links metabolism and BF
Occurs after a BV has been occluded for a short period
When occlusion released, BF rises above the pre occlusion level, and this period is maintained for roughly as long as occlusion was there.
What is the myogenic hypothesis?
Type of autoregulation
- Idea that Increased PP increases vascular pressure in circulation.
- the increased transmural pressure elicits SM stretch, causing them to contract, reduce flow
What is the metabolic hypothesis?
where is effect of mediators most felt?
Autoregulation
If a given organ is working harder, will demand more flow.
Causes vasodilation of arterioles to increase flow. Can not explain vasoconstriction in less metabolically active organs
Mediators: decreased pH important, lower; increased K+; ADP, AMP etc.
Effect mostly on pre capillary vessels, limited in post capillary ones.
Endothelial role in autoregulation
Endothelial cells are under more shear stresses at higher blood flows, release NO to vasodilate vessels.
(NO) synthetase
Some other integrative models proposed that play a role in local autoregulation
- low PO2, ATP released by RBC’s, acts on endothelium
- electrically activated vasodilation conducted rapidly upstream via endothelium
Distribution of sympathetic innervation
-Sympathetic adrenergic nerves supply all vascular beds, in both pre and post capillary areas.
Typically more in pre capillary, but extent of innervation varies among organ systems **
Review of sympathetic nerve terminal release
- Depolarisation at post ganglionic terminal- Ca2+ influx
- NE vesicles fuse with junctional membrane (are made by tyrosine hydroxylase-DOPA-dopamine-NE) and released in synaptic cleft (often with ATP)
- bind to a1 and a2 receptors (in periphery!)
a1 and a2 receptor differences **
a1: Is a GPCR (RQ), DAG leads to more Protein kinase C and protein phosphorylation; IP3 leads to increase iCa2+.
Are widely distributed. causes VC
a2: More sparse, Ginhibitory pathway (RI), less cAMP, less PKA, less Ca2+. Also K+ extrusion, hyperpolarises.Post synaptic = VC, pre synaptic modulates NE release
* Note B2 are similar, however Rs (Gs) original receptor, vasodilation
- Peripherally are autoreceptors, centrally decrease sympathetic drive
What are some inhibitory and excitatory examples of adrenergic transmission
autoreceptors?
Inhibitory: AcH, adenosine, dopamine, histamine, PGE1, E2
Excitatory: AII (increases gain of system, so more NE release when stimulated, also has own effect via AT1), adrenaline
Auto: a2 on pre junctional neuron. Stop NE release when NE binds
Cholinergic innervation of blood vessels
- largely parasympathetic
- leads to Ach in blood stream, which binds to M3 muscarinic receptors on endothelium. NO release and vasodilation
- in absence of enodthelium (damage) ACh binds to Muscarinic receptor on SM, VC
Effects of NE and E transfusion and subsequent note about receptor types in these organs
NE: decreased flow (VC) in Skeletal muscle, skin flow, kidney flow and splanchnic flow. Does not effect cerebral circulation. Indicating a1 receptors
E: increased flow in skeletal muscle and splanchnic flow; decreased flow in skin and kidneys. Indicates B2 receptors in muscle and gut vasculature
Affinities for alpha and beta 2 receptors by NE, E and isoprenaline
Consequence of this
Alpha: E>=NE»Isoprenaline
B2: Isoprenaline> Adrenaline» NE
Due to E higher affinity for B2 receptors, will cause VD in splachnic and skeletal muscle due to presence of pre capillary receptors of this kind.
B2 receptor structure
Note B2 receptor is Gs(stimulatory) via Rs andincreases cAMP and PKA causing Vasodilation
low affinity for NE
How does skeletal muscle increase its blood flow so high during exercise despite sympathetic drive seemingly counteracting by VC?
At rest sympathetic drive can divert blood flow.
Exercise induced local autoregulation by metabolites regulates
Circulating adrenaline from medulla binding to B2 receptors causing vasodilation
Inhibitors such as adenosine, histamine, PG’s block NT (reduce NE effectiveness from nerve)
Override NE release from nerve endings
Skin circulation and how it counteracts SNA during exercise, sustaining the BF?
- Affinity of receptors for NE decrease with local temperature increase
- Sympathetic cholinergic activation of sweat glands activates kinin cascade (neural control, not autoregulation)
- Bradykinin and lysylbradykinin dilate precapillary vessels, constrict post capillary vessels and increase capillary permeability
What can be said about cerebral autoregulation
- Precise autoregulation of blood flow between perfusion pressures of 60-180mmHg (not strictly true)
- Dominated by local factors
- Perivascular pH, pCO2, pO2 and [K+] important vasodilating metabolites
Effects of pO2 and pCO2 on cerebral flow (arterial O2)
pO2: blood flow does not chnage between 50 and 100mmHg. Below 50, increases blood flow
pCO2: Very quick effect, a small increase or decrease will alter flow. Low pCO2 very low blood flow, high higher blood flow, range of 25-60mmHg
Coronary blood flow how does it later
Heart controls, as heart works harder, increased metabolites leading to more flow.
Sympathetic innervation is present, but only will cause small changes at rest.
