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Autonomic Regulation of The Cardiovascular system. Cardiac

1.  Components of Regulation.

2.  Autonomic Component.

3.  Receptors.

4.  Cardiac, Vascular (Systemic Pulm).

5.  Comparative (anatomy).

6.  Assessment.

7.  Questions.

CARDIOVASCULAR FUNCTION: ADULT

• Transport Function

• Cardiac output= fH X SV

•  So Factors that alter -fH, or SV

• Fish – fH And SV

• Terrestrial vertebrates • Primary fH

CARDIOVASCULAR REGULATION

AUTONOMIC (Tone).

LOCAL /Hormonal

FEEDBACK CONTROL

Sympathetic Parasympathetic

Baroreflex

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REFLEXIVE CONTROL

4 6 8 10 12

20 s

Pres

sure

(kPa

)

Phenyl

Parasympathetic

Baroreflex

Chemoreflex

LOCAL

Sympathetic

Pharmacological Manipulation

LOCAL/HUMORAL MECHANISMS

• NO • Renin Angiotensin

• Prostaglandins • Catecholamines • 5HT • Endothelin • Hydrogen Sulfide • Adenosine • Histamine • NANC

• Auto regulation

AUTONOMIC COMPONENTS

•  Parasympathetic. –  Neurotransmitter-ACh

–  Cholinergic Receptors. Muscarinic/ nicotinic

•  Sympathetic –  Adrenergic receptors

•  α and β - ionotropic and Chronotropic

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AUTONOMIC COMPONENTS

•  Parasympathetic –  Cholinergic Receptors

•  muscarinic

Myogenic Vertebrate Heart

• Autonomous Depolarization

• Pacemaker tissue

• Sino atrial node • Sinus Venosus- Exp fish

Key- Cardiac tissue is a function syncytia-

Pacemaker tissue

• Na permeability- β adrenergic

• K permeability- Acetylcholine

• gN • gK • gCa

• gK • gCa

• gK • gCa

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Increase in Contractility

•  β1 Stimulation

• G protein

• Increase Ca++

•  Positive Inotropic

Sympathetic

EKG R-R interval Mammalian

Parasympathetic Tone

Sympathetic Tone

fH fH

CARDIOVASCULAR AUTOTONIC TONE-

Increased Contractility-β

Constant

Continuous

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CARDIOVASCULAR TONE Systemic Vasculature

Adrenergic Tone Vessels

β- receptors

α- receptors

VR

VR

Stimulated by:

Release from Sympathetic

Release from chromaffin tissue

CARDIOVASCULAR TONE Gas exchange Vasculature

Adrenergic -Vessels

β- receptors

α- receptors

VR

VR

Gills

Lung Adrenergic - Vessels

β- receptors

Amph,Reptilian Bird.

VR

Lung

VR Amph Reptiles

Cholinergic – Pulmonary Vessels

CARDIOVASCULAR TONE Gas exchange Vasculature

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1.  AUTONOMIC Tone Function.

2.  Vagus and Sympathetic nerves

a. Allows for precise changes in CO and arterial resistance. b. Meet metabolic demands

CARDIOVASCULAR TONE

Taylor and Wang 2009

Phylogeny of Cardiac Inneration

Peripheral Vessels

Adrenergic Innervation

?

Both α and β

Both α and β

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CARDIOVASCULAR TONE Anatomic Comparison

Elasmobranch

Parasympathetic- present Sympathetic - absent

Teleost Fish

Anatomic Comparison

Vago-sympathetic trunk Parasympathetic - present

Sympathetic – present lost in some species Possible Question What conditions allowed Loss

Amphibians

Vago-sympathetic trunk Parasympathetic - present Sympathetic - present

Anatomic Comparison

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Reptilian

Anatomic Comparisons Cont.

Parasympathetic - present Sympathetic - present

Mammalian (Avian) Anatomic Comparisons Cont.

Parasympathetic - present Sympathetic - present

Important Point: Anatomical Data Needs to Coupled to Pharmacological Data

METHODS OF ASSESSMENT

Ablation -Denervation -limited to cardiac innervation -Difficult in Fish and Amph.

Pharmacology -Drug Treatment- Involving Blockade, Depletion,

restricted release. -selective blockade can up-regulation other systems.

Direct Cardiovascular Measurements

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PHARMACOLOGY AS A TOOL OF INVESTIGATION

X X

X

Central

Peripheral

Drug X X

X

-Receptor Blockade -Ganglionic Blockade -Sympathectomy -Terminal depletion.

PHARMACOLOGY AS A TOOL OF INVESTIGATION

-Receptor Blockade- competitive antagonist A. Cholinergic - Atropine B. β-adrenergic- Proporanolol 1- 2- practolol C. α-adrenergic- phenotamine 1- prazosin 2- yohimbine -Ganglionic Blockade - Hexamethonium- nicotinic block

-Sympathectomy- 6-Hydroxydopamine storage impaired

-Terminal depletion- Reserpine

- inhibit release - Brytilium

EXAMPLE β-TONE ASSESMENT Receptor blockade

-60 -50 -40 -30 -20 -10 0

70 80 90 95 H

Δf H

(min

-1)

-0.6 70 80 90 95 H

-0.4 -0.2

0 0.2 0.4 0.6

ΔP m

ean(

kPa)

* * *

* *

* *

*

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SYMPATHECTOMY

Incubation Period (%)

1

2

3

4

5

P mea

n(kP

a)

70 80 90 95 H

150

200

250

300

350

f H (m

in-1

)

70 80 90 95 H

Pmean(kPa) fH (min-1)

WHAT IS THE SOURCE?

-60 -50 -40 -30 -20 -10 0

70 80 90 95 H

Δf H

(min

-1)

-0.6 70 80 90 95 H

-0.4 -0.2

0 0.2 0.4 0.6

ΔP m

ean(

kPa)

* * *

* *

* *

*

Crossley et al 2003

Incubation Period (%)

AUTONOMIC TONE Comparison

Elasmobranch - have adrenergic tone (cardiac and vascular);vagal tone cardiac

Teleosts- have adrenergic tone (cardiac, vascular) vagal tone (cardiac).

No sympathetic innervation

Amphibians- have adrenergic tone (cardiac, vascular) vagal tone (cardiac and pulmocutaneous vessel).

Reptiles- have adrenergic tone (cardiac, vascular) vagal tone (cardiac and pulmonary artery vessel).

Mammals and Birds - have adrenergic tone (cardiac, vascular) vagal tone (cardiac).

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Interprate this Finding

fH antagonist - fH control fH intrinsic •  1. Questions

– How does Each tonus Compare?

– How does Activity effect tonus?

– How does Species compare?

– How do Animals Compare at different Life Stages

–  Ect.

TONE CALCULATION

Sympathectomy/Ganglionic

- 6-Hydroxydopamine

- Hexamethonium

PHARMOCOLOGY: Drugs and