Humoral and local control Lecture 10

Question 1

List the influences on blood vessels in vivo

Answer 1

Myogenic tone (ABP) - strech of blood vessels from within

Sympathetic noradrenergic

Endothelium derived substances

Hormones, O2, CO2 etc in blood

Substances released from tissue cells that accumulate in the interstitial space

Question 2

Describe the hormonal influences on blood vessels

Answer 2

Catecholamines- adrenaline, noradrenaline- released from the adrenal medulla in response to environmental stressors, strenuous exercise, cold etc

NA- weak of all arterioles except cerebral- stimulates alpha2 receptors➡️ NO synthesis and increase cGMP

Adrenaline- vasodilation in skeletal muscle only- beta2 receptors occur on VSM and endothelial cells- stimulates NO synthesis and increasing cAMP -vasoconstriction in all other vessels (alpha receptors)

ADH- released by pituitary gland- acts on V1 receptors on VSM- vasoconstriction

Angiotensin2- acts in AT1 receptors on VSM- vasoconstriction

Question 3

Summarise local influences on blood vessels

Answer 3

Blood flow is regulated by local mechanisms to support tissue metabolism- ‘flow-metabolism coupling’

Little variation in skin (high resting metabolism and tissue O2 consumption) and kidney (high resting metabolism and tissue VO2)

Can vary a lot in skeletal muscle (maximally dilated during exercise and dilated within systemic hypoxia. In these circumstances local dilators overcome contrictors), cardiac muscle and brain (all have large scope for increasing metabolism in exercise, cardiac work is increased) (brain capacity increase in limited by skull)

Question 4

Describe the response to system hypoxia

Answer 4

Fall in PaO2 affects endothelial cells- Release adenosine➡️ stimulates NOS to form NO and COX to form PGI2

Fall in PaO2 affects RBCs- release ATP when O2 is offloaded via pannexin channels. ATP produces vasodilation via P2Y receptors on endothelial cells which triggers pathway

ATP metabolised by ecto-nucleotidases to ADP, AMP and adenosine which acts on endothelial P1 receptors

Vasodilation increases blood flow and shear stress which further stimulates NO Fall in PaO2 also inhibits vasoconstrictors

Question 5

Describe the response to muscle hypoxia

Answer 5

Muscle contraction causes

1. K efflux during repolarisation of muslce action potentials- vasodilator
2. ATP release- metabolised by ectonucleotidases to adenosine
3. ATP degradation also produces inorganic phosphate
4. Synthesis and release of PGE2

Dilation caused by K induced hyperpolarisation which closes Voltage gated Ca channels on VSM

Adenosine acting in VSM P1 receptors

PGE2 acting in EP receptors

RBC release O2 and ATP which may induce dilation via endothelial P2Y receptors

Vasodilation increases shear stress which stimulates NO production

Dilator infleunces blunt vasocontrictor effects of sympathetic transmitters NA/ATP - functional sympatholysis

Question 6

Summarise coronary circulation

Answer 6

3-4% of cardiac output

Cardiac muscle exracts 70-80% of O2 from each ml of blood when body at rest

Has high VO2 under resting conditions

Coronary arteries are more dilated than skeletol muscle arterioles.

INcreased cardiac work needs more O2, increased blood flow needed by cononary vasodilation

Question 7

Summarise the Berne hypothesis

Answer 7

Is when cardiac muscle had low intraceullar PO2 under resting conditions

A further fall in intracellular PO2 causes AMP to form Adenosine (Produced by endonucleotidases from AMP)which causes vasodilation and is manly responsible for matching O2 delivery to VO2 in cardiac muscle and coronary blood flow

Coronary vessles have sympathetic noradrenergic nerve supply and can cause an increae in blood flow due to increase heart rateand contractility which increase work nd vasodilation occurs

Parasympathtic nerves causea decrease in blood flow due to it causeing decreased heart rate and then vasocontrcition.

Question 8

Summarise cerebral circulation

Answer 8

Increased neuronal activity requires more O2 and glucose

Mostly by increasing delivery by vasodilation which has to be compensated by vasoconstriction elsewhere to prevent increased intracranial pressure

Responses to changes in local CO2 are thought to occur by stimulation of prostaglandin synthesis

Responses to local O2 occur via adenosine, prostaglandins and NO via the endothelium

Question 9

Summarise glial cell function with cerebral blood flow

Answer 9

Interneurones release glutamate

Glial cells siphon up K+ released by neurones and release K+ near arterioles which cause the hyperpolarisation of VSM which causes vasodilation

Glial cells also synthesise and release prostaglandins and adenosine - other vasodilators