Autonomic Regulation Of CVS

Question 1

What is peripheral vascular resistance

Answer 1

Vascular resistance to the flow of blood in peripheral arterial vessels that is typically a function of the internal vessel diameter, vessel length and blood viscosity

Question 2

What does peripheral vasculature do?

Answer 2

Controls local flow and selectively distributes CO to various organs and tissues
-simultaneous max flow through all organs and tissue should exceed max CO available
-all vessels have some degree of basal tone and there is active vasoconstriction of most vessels

Question 3

What is vasomotor tone (resistance)

Answer 3

Sum of basal tone plus constrictor/dilator influences
Balance of such influences varies between different vascular beds

Question 4

How is vasomotor tone controlled?

Answer 4

Extrinsic influences
-nervous control, circulating hormones (adrenaline, angiotensin 2)
Intrinsic influences (local processes in tissue)
- myotonic response (depolarisation in response to stretching), temperature ,tissue metabolites, locally released mediators

Question 5

All signals ultimately modulate ……

Answer 5

Calcium

Question 6

Why do signalling mechanisms regulate calcium?

Answer 6

Vasoconstrictors elevate intracellular calcium
Vasodilators lower intracellular calcium
Regulation of external calcium entry/exit or mobilisation of intracellular calcium stores
Involvement of receptor-operated ion channels and GPCR/second messenger pathways

Question 7

Nervous control:sympathetic vasoconstriction

Answer 7

Sympathetic vasoconstrictor fibres innervate most blood vessels - important influence on BP
Noradrenaline released from postganglionic nerves - together with co-transmitters/neuromodulators (ATP, neuropeptide Y)

Question 8

Co-transmitters in sympathetic vasoconstriction

Answer 8

Are released with noradrenaline and exert direct action on smooth muscle contraction

Question 9

Neuromodulators

Answer 9

Have no direct action on contraction but potential action of other neurotransmitters

Question 10

Describe sympathetic nerves

Answer 10

Terminal portions of sympathetic nerves branch and form network over surface of blood vessel, may penetrate outer layers
Each branch may contain varicosities packed with NT
Receptors widely distributed over tissue surface

Question 11

Distribution of adrenoreceptors and functional effects

Answer 11

Effector organ: Heart
Rate of contraction, cardiac conductivity, force of contraction - all increased. Receptor - B1
Effector organ: Blood vessels
Arteries (arterioles) - constriction - a1
Skeletal muscle/periphery - dilation - b2
Veins - constriction - a1

Question 12

Examples of NANC transmitters in peripheral nervous system

Answer 12

Dopamine, substance P, ATP, 5HT, NPY, CGRP, VIP

Question 13

What are NANC transmitters and where are they released

Answer 13

Non-andrenergic non-cholinergic transmitters
Mainly released from the same terminals as classical transmitters (co-transmission)
Occasionally contained in local inter-neurones activated by acetylcholine released from pre-ganglionic autonomic neurons

Question 14

What is co-transmission

Answer 14

Co-transmitters may differ in rates of activation - temporal altercations in character of overall response
Ratio of released transmitters may vary with stimulation frequency - differential release/response
Release may be differentials regulated at pre-synaptic level - B2 adrenoreceptor activation increased NA release but decrease ATP release

Question 15

3 classifications of presynaptic interaction

Answer 15

Homotropic
Heterotrophic
Neuromodulation

Question 16

Describe homotrophic interaction

Answer 16

Auto inhibitory feedback of transmitter itself
Quantified by antagonism of pre-synaptic auto receptors
Many noradrenergic and cholinergic terminals

Question 17

Describe heterotrophic interaction

Answer 17

Released transmitter interferes pre-synaptically with release of other transmitters
Especially in myenteric plexus and heart (NA/ACh)
Noradrenergic/cholinergic nerve terminals in the heart

Question 18

Describe neuromodulation

Answer 18

Substances produced locally in target tissues (and glia?) regulate transmitter release (NO, PGs)

Question 19

A1 adrenorecptor antagonists prevent…

Answer 19

Vasoconstriction by noradrenaline
Effects of noradrenaline are further reduced by negative feedback since pre-synaptic a2 andrenoreceptors are not blocked and can still be occupied by noradrenaline to activate a negative feedback pathway

Question 20

Inhibitaory influences on noradrenaline release from sympathetic nerve endings (receptor type/mediator)

Answer 20

A2 adrenoreceptors/noradrenaline
5HT1 receptor/serotonin
P1 receptor /adenosine

Question 21

Facilitatory influences on noradrenaline release from sympathetic nerve endings

Answer 21

B2 adrenoreceptor / adrenaline
AT receptors / angiotensin 2

Question 22

Describe the baroreceptor reflex

Answer 22

• arterial baroreceptors are sensitive to stretching of walls of vessels in which nerve endings lie
• ↑ stretching ↑ firing rate of receptors
• carotid sinus receptors respond to pressures from 60-180 mmHg
• aortic arch receptors have > threshold pressure, less sensitive so carotid sinus receptors normally dominant
• maximal carotid sinus sensitivity occurs near normal mean arterial pressure
• this “set point” changes during chronic hypertension (less sensitive, higher activation threshold)
• receptors are sensitive to rate of pressure change as well as mean pressure
• under normal physiological conditions, baroreceptor firing exerts tonic ↓influence on sympathetic outflow from medulla
• hypotension results in disinhibition of cardiovascular centre in medulla:
• ↓ arterial pressure (mean, pulse or both)↓ baroreceptor firing
• cardiovascular centre responds by ↑sympathetic and ↓ parasympathetic outflow

Question 23

SNS activity is ……. In salt and obesity-induced hypertension

Answer 23

Enhanced

Question 24

Strategies to target influence of SNS

Answer 24

Pharmacological inhibition
- alpha 1 and beta adrenoreceptor antagonists, alpha 2 agonists, noradrenaline store depletes, adrenergic and ganglion neuron blockers
Device-based inhibition
- carotid baroreceptor activation, renal sympathetic enervation

Question 25

Nervous control: parasympathetic vasodilator nerves

Answer 25

Most blood vessels do not have significant parasympathetic innervating
Targets include cerebral and coronary arteries, erectile tissue, salivary glands, intestinal mucosa, exocrine pancreas
Release acetylcholine (acting on muscarinic receptors) and co-transmitters (VIP, NO)

Question 26

Co- transmission

Answer 26

Neurons can release more than one transmitter or modulator, each interacts with specific receptors and produces distinct effects
Eg parasympathetic innervating of salivary gland

Question 27

Describe co-transmission and parasympathetic innervation of salivary gland

Answer 27

Acetylcholine stimulates exocrine secretion
VIP stimulates regional vasodilation required to sustain fluid secretion from gland
Leading to a co-ordinated response

Question 28

Hormonal control: adrenaline - released from and action

Answer 28

Released from neuroendocrine chromaffin cells in adrenal medulla (modified sympathetic ganglion) into bloodstream (secrete adrenaline:noradrenaline 5:1)
Similar to sympathetic nerve activation but : non-sympathetically innervated cells can respond; effects prolonged due to prolonged release and slow removal from blood
Vasodilation of skeletal muscle arteries at physiological concentrations [B2]

Question 29

Intrinsic mechanisms

Answer 29

Myotonic response
Local temperature

Question 30

Myotonic response

Answer 30

Increased pressure increases contraction
Stretch-operated ion channels

Question 31

local temperature

Answer 31

Temp <10 degrees exerts inhibitory influence
Reduction in temperature enhances a2 adrenoreceptor activation, reducing noradrenaline release

Question 32

Describe metabolic vasoactive factors

Answer 32

Functional/metabolic hyperaemia
Acidosis
Hypoxia
Adenosine
Interstitial potassium
Phosphate ions
Hyperosmolarity

Question 33

Describe locally-released mediators

Answer 33

Endothelium-derived nitric oxide - released in response to sheer stress, hypoxia, inflammatory autocoids
Local autocoids (often associated with inflammatory response) - histamine, bradykinin, eicosanoids