CS 2015

Neural Regulation ofBlood Pressure

Christian StrickerAssociate Professor for Systems Physiology

ANUMS/JCSMR - ANU

Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/BPControl.pptx

THE AUSTRALIAN NATIONAL UNIVERSITY

CS 2015

CS 2015

Aims

At the end of this lecture students should be able to

• locate sensors, integrators & effectors of the reflexes;

• outline the anatomy of the reflex pathways;

• contrast the nature and effect of the arterial baroreflex

(AB) and the cardiopulmonary reflexes (CP);

• explain how AB controls HR, SV and TPR, and CP

mainly venous return;

• recognise how AB establishes beat-to-beat control; and

• point out how these reflexes can be modulated by

respiration and asphyxia/shock.

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Contents• Overview of control of blood pressure

– Principles of negative feedback

– Regulated variables

• Arterial baroreflex (AB)– Components: detectors (high pressure baroreceptors) and

afferents, efferents (sympathetic and parasympathetic

output to cardiovascular system), integrator.

• Cardiopulmonary reflexes (CP)– Low pressure baroreceptors

– Atrial stretch and release of ANP

• Respiratory and chemoreflex modulation of

baroreflex activity.

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Topic Coverage

• In this session, we ONLY look at BP control on the

short-term (seconds).

• Long-term BP control via volume control will be done

in relation to kidney (see later “Volume regulation”).

• How vessels locally regulate resistance will be the

subject of the next lecture.

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Overview of BP Control• In Block 1, mean arterial pressure was defined as

is mean arterial pressure (MAP), TPR total peripheral

resistance, CO cardiac output, SV stroke volume and HR

heart rate.

• controlled by 3 variables: TPR, SV and HR.

• Which system can control these parameters?– Autonomic nervous system:

• HR: sympathetic (+), parasympathetic (-; vagal) at heart

• SV: sympathetic (+), parasympathetic (-; but not muscle!) at heart;

sympathetic (+) at TPR (afterload); and others.

• TPR: sympathetic (+) ONLY at vessels (& other factors like volume, etc.).

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Principles of Feedback Control

• Positive and negative feedback.

• Feed-forward: central command before exercise starts.

• Functional characteristic is feedback time: from few

100 ms to hours or even longer.

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Overview of Reflex Control

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• Two feedback reflexes involved:– arterial baroreflex (AB – sympathetic and parasympathetic) and

– cardio-pulmonary reflexes (CP – at large sympathetic only).

• Modulated by respiration.

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Arterial Baroreceptor Reflex (AB)

• Most afferent input is excitatory.

• Mostly negative feedback to brainstem, sympathetic

nervous system and heart: Depressor reflex.• If BP↑ → HR↓, SV↓, TPR↓ and vice versa if BP↓.

• Most important contributor to short-term homeostatic

control of BP (s - min).

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Locations of AB Sensors

• Pressoreceptors in aortic arch and carotid sinus.

• Afferent nerves: IX (carotid sinus) & X (aortic arch).

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• True mechanoreceptors (wall tension in vessel).

• Sensitive over large BP range– Normal pressure range: A-fibres; high pressure range: C-fibres.

– Linear response in “normal” range.

– Respond better to pulsatile than steady pressure: adaptation

under steady (static) conditions, much less under pulsatile

(dynamic): poor at relaying absolute BP information.

AB Sensor Properties

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AB Set-Point and Sensitivity

• Set-point = maximal slope in

HR vs BP plot.

• Max. sensitivity 80 – 100 torr.

• Exercise resets set-point:

work in higher range without

incurring depressor

response; i.e. at same BP, a

higher HR can be achieved.– Reset in proportion to work

intensity.

– AB active but HR is permitted

to increase (muscle spindles).Levy, 5th ed., 2010

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AB Efferent Activity

• SY output over whole sympathetic

chain (T1 – L3).

• Parasympathetic output via VA and

lumbosacral cord (S2 – S4).

• Both systems are activated wholly.

• VA and SY outputs act together but

in opposite directions:– VA↓ → SY↑ or

– VA↑ → SY↓.

• For > 180 torr, VA is maximised

and SY minimised.

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• Control area in brainstem (several nuclei) receives input

from / sends outputs to many brain parts (hypothalamus).

• VA relay simpler (NTS → NA) than that of SY pathway.

Le

vick

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Central AB Pathways

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Medullar Interactions

• VA → SY inhibition (dashed lines) via – caudal inhibiting rostral vasopressor area (via GABA) and

– raphe nucleus to spinal cord (via serotonin).

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AB Function

• AB helps to stabilise BP control beat by beat (fast response

– VA!) within narrow range – if taken away, BP fluctuates

widely.

• Effect via coordinated VA↑ and SY↓ activity when BP↑: HR↓,

SV↓ and TPR↓ and vice versa.

• VA and SY work together but in opposite direction.

• During exercise, set-point shifted such that BP can rise

without HR inhibition.

• Modulated via inputs from respiratory & other centres.

• Activated in orthostasis, dehydration, blood loss (shock) etc.

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Cardiopulmonary Reflexes (CP)

• Collection of various reflexes based on

sensor types.

• Low-pressure receptor reflexes.

• Most afferent input is inhibitory.

• Work predominantly on VR – mostly SY

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Cardiopulmonary Reflexes (CP)

1. Cardiac de-afferentiation (transplant) reveals tonic

inhibition of HR and TPR only: Inhibitory cardiac afferents– Intracoronary injection of solute causes bradycardia, vasodilation and

hypotension:• Depressor reflex: HR↓, BP↓, TPR↓.

2. Important to know some specific reflexes as some can

cause only SY↑ activity:- Activation of veno-atrial stretch receptors causes tachycardia and

diuresis.• Sympathetic only reflex on SAN/volume regulation: HR↑ and central volume.

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Locations & Types of CP Sensors

Le

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• Heart sends off mostly small, unmyelinated (80%) fibres from– cardiac mechano-receptors (wall tension in ventricle);

– ventricular chemosensors (mediate pain via SY fibres): SY activity↑;

– coronary artery baroreceptors (perfusion pressure); and

• Some myelinated (20%): veno-atrial mechanoreceptors (type A/B).

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Veno-Atrial Stretch Receptors• Measure atrial blood volume, i.e. central venous

pressure/volume in low pressure part of circulation

(central veins, atria); control venous return (VR).

• Upon activation (via infusion - ‘Bainbridge effect’)– SY activity↑ to SA node (tachycardia) without change in

VA activity; and

– diuresis and natriuresis: control of blood volume via renal

vasodilation (renal Na+ excretion↑), anti-diuretic hormone

release↓ (hypothalamus) and release↑ of atrial natriuretic

peptide (ANP) by atrial cells.

• Part of long-term volume regulation response (see

volume control in kidney section, later).

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Modulation by Respiration &

Arterial Chemoreceptors

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Respiratory Modulation of HR

• During inspiration, HR↑:– Inspiratory centre inhibits

vagal output (motoneurones

shortly unresponsive to AB

input) → disinhibition of SA

node → HR↑.

• Converse is true during

expiration.

• Emotional faint: VA output↑

→ HR↓↓.

Levick, 5th ed., 2010

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Role of Arterial Chemoreceptors

• Carotid and aortic bodies (see respiration, later): sense

predominantly and , but also some pressure.

• Send inhibitory input to the brainstem.

• If < 80 torr (asphyxia, clinical shock, …):– Tachycardia due to resp. rate ↑ (lung stretch receptors inhibit

VA output) → SY↑.

– TPR↑ as renal, splanchnic and muscle vascular beds constrict;

– Splanchnic veins constrict → pooling↓ → SV↑ → CO↑.

– BP↑ as TPR↑ and CO↑.

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Take-Home Messages• Under resting conditions, VA output on heart is more effective

than that of SY.

• Both, VA and SY nerves are tonically active and oppose each

other; VA effect is fast, SY effect appreciably slower.

• AB provides important short-term regulation of BP:– If BP↑, high pressure receptors in aortic arch and carotid sinus cause

HR↓, SV↓ and TPR↓ and vice versa.

• Cardiac de-afferentiation reveals tonic inhibitory effect on HR and

TPR – part of CP reflexes.

• Veno-atrial stretch receptors HR↑ and help control BP mainly via

circulating blood volume↓ → VR↓; i.e. renal vasodilation,

hypothalamic release↓ of ADH and atrial release↑ of ANP.

• When BP falls < 80 torr, peripheral chemoreceptors modulate BP

via vasoconstriction plus tachycardia.

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MCQJack West, a 28 year-old bike rider was involved in a car accident on the

road to the snowfields. He suffered a broken femur and was immediately

transferred to Cooma Base Hospital. On admission, his HR was 112 bpm,

and his blood pressure 65 / 45 torr. Which of the following statements best

describes the state of the arterial baro- and cardiopulmonary reflex?

A. Arterial baroreceptor activity↓; sympathetic outflow↓;

parasympathetic outflow↑; low pressure mechanoreceptor activity↓.

B. Arterial baroreceptor activity↑; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↓.

C. Arterial baroreceptor activity↓; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↓.

D. Arterial baroreceptor activity↑; sympathetic outflow↓;

parasympathetic outflow↑; low pressure mechanoreceptor activity↑.

E. Arterial baroreceptor activity↑; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↑.

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That’s it folks…

CS 2015

MCQJack West, a 28 year-old bike rider was involved in a car accident on the

road to the snowfields. He suffered a broken femur and was immediately

transferred to Cooma Base Hospital. On admission, his HR was 112 bpm,

and his blood pressure 65 / 45 torr. Which of the following statements best

describes the state of the arterial baro- and cardiopulmonary reflex?

A. Arterial baroreceptor activity↓; sympathetic outflow↓;

parasympathetic outflow↑; low pressure mechanoreceptor activity↓.

B. Arterial baroreceptor activity↑; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↓.

C. Arterial baroreceptor activity↓; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↓.

D. Arterial baroreceptor activity↑; sympathetic outflow↓;

parasympathetic outflow↑; low pressure mechanoreceptor activity↑.

E. Arterial baroreceptor activity↑; sympathetic outflow↑;

parasympathetic outflow↓; low pressure mechanoreceptor activity↑.