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L10 Humoral and Local Control of Blood Vessels
Humoral – anything not due to sympathetic or parasympathetic
Effects of sympathetic nerve activity varies between tissues
Strong sympathetic activity
 Skin
 In skeletal muscle, can be blunted by local dilator influences – changes in tissue metabolism
 In kidney, in competition with pressure autoregulation
 In cerebral, in competition with pressure autoregulation and local influences
 Coronary usually overcome by local metabolic influences
 Pulmonary usually overcome by pressure-dependent effects of local PO2
Weak sympathetic activity
Influences on blood vessels in vivo
 Myogenic tone (ABP)/intravascular pressure –
pushing outwards on wall (more stretch
vasoconstriction)
 Sympathetic noradrenaline – tone =
constantly slightly constricted
 Endothelium-derived substances
 Hormones, O2, CO2, etc in blood
 Substances released from tissue cells that
accumulate in the interstitial space
o i
...
mixture of vasodilators and vasoconstrictor influences that interact with one another and that are
changed in different conditions
Hormonal Influences
Generalised effects on blood vessels in all tissues
 Catecholamines: Ad & NAd – released from adrenal medulla in response to environmental stressors, strenuous
exercise, cold etc
o NAd – weak constriction of all arterioles excepts cerebral (α1 receptors on VSM)
 V
...
g
...
But large scope for regional increases in blood flow within brain tissue where neuronal activity is
increased
...
Fall in PaO2 affects endothelial cells
a
...
Stimulates COX  PGI2
2
...
Release ATP when O” is unloaded from Hb (change shape  lose ATP_
b
...
ATP is also metabolism by ecto-nucleotidases to ADP, AMP and adenosine – acts on endothelial P1 recs
4
...
Dilator influences blunt vasoconstrictor effector sympathetic transmitter NAd/ATP – hypoxic sympatholysis
(prevent vasoconstriction from smyp nerves)
Wen RBCs offload oxygen from Hb, ATP, is released from the RBC – ATP acts on P2Y receptors on endothelial cells to
induce local dilation and dilation is conducted up the arterial tree via VSM
Local regulation of Skeletal muscle circulation in exercise
 During, exercise muscle VO2
increases in proportion to work
load until VO2 max
 Muscle O2 extraction from blood
increases to ~80% of O2 delivered
to it
 Consequently, there is a large
gradient for O2 from blood to
muscle
o Therefore, muscle PO2
falls from ~27mmHg to at rest to 2-3mmHg makes a large gradient between blood and muscle
o Whereas PaO2 remain constant maintained by increased VE
o Arteriolar dilation occurs which is proportional to work load and helps to increase blood flow and O2
delivery
Muscle contraction causes
1
...
ATP released from skeletal muscle fibres – metabolised by ecto-nucleotidases to adenosine (adenosine
acting VSM P1 receptors)
3
...
NB
4
...
Glucose
delivery i
...
vasodilation
o Cerebral arterioles are very sensitive to changes in local O2 and CO2 as well as to locally released
metabolites
o Any increase in gross cerebral blood flow is restricted by skull
o Vasodilation occurs regionally: “compensated by reduction in blood flow elsewhere in brain
 Extra cerebral arterial vessels run over surface of brain and then branch into brain tissue to form capillaries
Responses of cerebral circulation to changes in CO2 and O2
 Vasoconstrictor/Dilator responses to changes in local CO2 are thought to occur by
o Changes in stimulation of synthesis of dilator prostaglandins - After CO2 crosses blood brain barrier
(capillary endothelium)
o Dilator responses to changes in local PO2 occur via
 Adenosine, prostaglandins and NO via endothelium – which cross blood brain barrier to act on
VSM
o Brain arterioles also response to substances released by glial cells
o Arterioles are more responsive to CO2 partial pressure
 CO2 is a result of oxidative metabolism
Cerebral Flow-metabolism coupling
 Glial cells form a network with end-feet on arterioles and neurones
 During changes in neuronal activity:
o Neurones release K+
o Glial cells siphon up K+ and release K+ at other end of cell close to supplying arterioles
o K+ causes hyperpolarisation of VSM
o Glial cells also synthesis and release other vasodilators:
 Prostaglandins + Adenosine
o Allows very tight coupling between neuronal activity and supplying arterioles



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