Autonomic nervous system: cardiovascular integration

Question 1

Cardiovascular revision

Answer 1

see structure diagram

Cardicac output:
- defined as the total amount of blood pumped by one side of the heart per unit time (min)
- Essentially it is the measure of flow per minute)
- at rest: ~5 L /min / during exercise: ~35 L /min
*CO = SV x HR
*MABP = CO x TPR

Pressure
*MAP = CO x TPR
*TPR -dependent on radius blood vessel (1/r4)
*Largest pressure drop occurs in the arterioles, the site of the major resistance to blood flow
*Arterioles innervated by sympathetic nerves

Question 2

Cardiac revision: How is flow controlled

Answer 2

Extrinsic- reflexes determine blood flow to organs
*Sympathetic fibres innervate tunica external /external elastic lamina (shown in yellow in left diagram)
*Neurotransmitters influence smooth muscle

Intrinsic- regulation at organ (this is currently being debated and may be more extrinsically influenced)

Question 3

Organisation of the ANS sympathetic and parasympathetic

Answer 3

In the sympathetic pathway:
- sympathetic systems all originate in sympathetic pre-ganglionic neurons from the spinal cord, synapse with a neuron and deliver to an organ with the exception of the adrenal gland
- Pre-ganglionic neuron is relatively short and post-ganglionic neuron is relatively long.
- Ganglia chain is located around the spinal column. Ganglia originate in the thoracic and lumber regions.

In the Parasympathetic pathway:
Pre-ganglionic neuron is relatively long and post-ganglionic neuron is relatively short.
Ganglia is located on or near effector. Ganglia originate in the brain stem and sacral regions.

(see diagrams)

Question 4

Basic characteristics of sympathetic and parasympathetic ANS function

Answer 4

The pre-ganglionic neurons of both systems secrete acetylcholine. Sympathetic post ganglionic neurons release norepinephrine and parasympathetic post ganglionic neurons release acetylcholine.

Heart, lungs and GI tract are innervated by both branches of the ANS.

Sympathetic increases heart rate, relaxes bronchioles and prevents release of bile and digestion processes

Parasympathetic reduces heart rate, stimulates bronchiole constriction and triggers release of bile and digestion processes

Question 5

Some ANS effects on the heart:

Answer 5

*Sympathetic (NA) -tachycardia
*AM circulating (A) -tachycardia
*Parasympathetic (Ach) -bradycardia
*Vascular Resistance
*NA constriction increase in vascular resistance
*A dilatation decrease in vascular resistance
*ACh (muscarinic) dilatation decrease in vascular resistance

Question 6

Extrinsic control with the ANS:

Answer 6

*Baroreflex
*Bainbridge Reflex
- HR changes related to blood volume changes without a change in BP
*In practice both reflexes active
* see Berne & Levy Chapter 17 pages 325-326

Question 7

Baroreceptor – reflex and modulation: Arterial pressure control

Answer 7

automatic reflex aka the baroreflex (pressure reflex)

Acts by changing heart rate when blood vol changes without changing blood pressure
*Baroreceptors (high pressure receptors)
*Carotid arch (carotid sinus)
*Aortic arch
*Stretch arterial wall
*Afferent pathway to nucleus tractus solitarius (medulla)
*Efferent pathway- autonomic nervous system adjust BP accordingly
-abnormal or lack of control usually results in heart failure

Baroreceptor response to pressure:
*Carotid sinus baroreceptors not stimulated by pressures between 0 ~50 mmHg
*50+ mmHg respond progressively more rapidly, maximum ~180 mmHg
*Aortic receptors operate +30 mmHg above
*Sensitivity

Question 8

Pressure “buffer” function of the baroreceptors

Answer 8

*Buffer against changes in pressure so over long term ~ constant
*Dog -24 hours well controlled (normal activities)
*Denervate extreme variability (normal activities)
*24 hr recording
*Primary purpose baroreceptor system reduce minute by minute variation in arterial pressure

see diagrams for the baroreflex

Question 9

Resetting due to a sustained change in arterial blood pressure

Answer 9

1.The baroreceptor reflex will reset to the right in response to a sustained increase in arterial blood pressure, and to the left in response to a sustained fall in arterial blood pressure

2.Acute resetting begins to occur within 5 mins and is essentially complete within 20 mins of the change in arterial pressure.

3.Acute resetting is due to the modulation of the afferent limb of the baroreceptor reflex

Question 10

Central nervous pathways controlling arterial blood pressure

Answer 10

see diagram

Question 11

Stimulation of RVLM – changes in BP

Answer 11

see diagrams
*NTS complex nucleus, receives numerous sensory inputs
*Viscerotopic organisation of both afferent inputs and efferent outputs
*Chemical stimulation of RVLM results in changes in BP

Question 12

Local (intrinsic) control of peripheral blood flow

Answer 12

1.Autoregulation
2.Myogenic Mechanism
3.Metabolic Regulation
4.Endothelium-Mediated Regulation

Question 13

Local (intrinsic) control of peripheral blood flow:
1. Autoregulation

Answer 13

1. Autoregulation
   *Certain tissues blood flow adjusted to the existing metabolic activity of the tissue
   *Tissue metabolism steady, changes in perfusion pressure (arterial pressure) evoke vascular resistance changes that tend to maintain a constant blood flow

*Skeletal muscle preparation -completely isolated from rest of animal and is in resting state
*Control pressure 100 mmHg.
*Expt:Increase & decrease pressure
*Blood flow observed immediately after changing perfusion pressure (closed circles)
*Maintenance of altered pressure at each new level followed within 30- 60 seconds by a return of flow toward control levels (open circles)
*Steady state flow
*20-120 mmHg steady state flow relatively constant
*Resistance across vascular bed shows resistance vessels constrict with elevation of pressure & dilate with the decrease pressure

Why does blood flow remains constant in presence of an altered perfusion pressure ?

Myogenic mechanism - vascular smooth muscle contracts in response to an increase in pressure difference across the wall of a blood vessel (transmural pressure) and relaxes in response to a decrease in transmural pressure.

Question 14

Local (intrinsic) control of peripheral blood flow:
2. Myogenic regulation

Answer 14

see diagram:
A. Arterioles isolated from hearts young pigs & cannulated each end.
Transmural pressure (intravascular pressure - extravascular pressure) & flow through the arteriole could be adjusted to desired levels.

B. No flow: successive increases of transmural pressure elicited progressive decreases in vessel diameter-constrictor response -as pressure rises vessel constricts to maintain flow at steady state conditions

C. response in B independent of endothelium because it was identical in intact vessels and in vessels that had been stripped of endothelium. Arterioles relaxed by direct action nitroprusside (NO donor) on vascular smooth muscle show passive increase in diameter with increase transmural pressure.

Mechanism: Stretch vascular smooth muscle has been shown to raise intracellular Ca2+, the increase in transmural pressure believed activate membrane calcium channels

BP normal maintained fairly constant baroreflex so myogenic probably ineffective under normal conditions

Importance: probably when moving from lying to standing position. Increase in transmural pressure causes constriction help maintain BP (transient effect?)

Question 15

Local (intrinsic) control of peripheral blood flow:
3. Metabolic regulation

Answer 15

Metabolic regulation

*Blood flow in a given tissue is governed by the metabolic activity of the tissue. Any intervention that results in an inadequate O2 supply prompts the formation of vasodilator metabolites.

*The metabolites are released from the tissue and act locally to dilate the resistance vessels.

*When the metabolic rate of the tissue increases or the O2 delivery to the tissue decreases, more vasodilator substance is released.

Candidate vasodilator substances
*Lactic acid, CO2, H+: Decrease in vascular resistance induced by supernormal concentrations of these dilator agents is substantially less than the dilatation observed when metabolic activity is increased physiologically.
*K+, inorganic phosphate ions, interstitial fluid osmolarity: May contribute to active hyperaemia (increased blood flow caused by enhanced tissue activity).
*Increase phosphate, osmolarity not consistently observed during muscular activity.
*K+ released onset skeletal muscle contraction. Could be responsible initial decrease vascular resistance. Release not sustained.
*Adenosine, prostoglandins: Coronary blood flow + skeletal muscle

Does metabolic control exist?
*Metabolic control of vascular resistance by the release of a vasodilator substance?
*Predicted existence of a basal vessel tone -muscle tone independent of nervous system.
*Metabolic factor must be responsible for maintaining tone
*Reactive Hyperaemia: to test for existence of local metabolic factor that regulates tissue blood flow.

Question 16

Intermittent claudication (thromboangiitis obliterans)

Answer 16

*Disease arterial wall -obstruction artery have intermittent claudication if disease in legs.
*Leg pain when subject walks or climb stairs. Pain relieved by rest.
*Smokers (men)
*Minimal walking, resistance vessels become maximally dilated by local metabolite release.
*When O2 demand of muscle increases with more rapid walking, blood flow cannot increase sufficiently to meet muscle needs for O2, and pain caused by muscle ischaemia results

Question 17

Local (intrinsic) control of peripheral blood flow:
4. Endothelium mediated regulation

Answer 17

*Stimulation of endothelium can elicit a vasoactive response of the vascular smooth muscle

*A) transmural pressure constant, flow increased –> vasodilatation

*Stimulation of endothelium can elicit a vasoactive response of the vascular smooth muscle

*B) vasodilatation caused by release nitric oxide (NO) from endothelium in response to shear stress caused by increase in flow. Arteriole striped endothelium response to flow abolished.

*Role of adenosine in dilator responses induced in arterioles by systemic hypoxia

*Respiratory & cardiovascular response evoked in anaethetised rat breathing 8% O2 for 5 min before and after 8-phenyl theophyline (8-PT) was given systemically.

see diagrams

Question 18

Summary

Answer 18

*Systemic administration 8-PT reduced fall in ABP and increase in FVC in resting hindlimb muscle that was induced by systemic hypoxia.
*Topical application 8-PT to spinotrapezius muscle reduced dilator response induced in arterioles of that muscle by systemic hypoxia.
See: Mian & Marshall, (1991) J. Physiol. 443; 499-511.

*Systemic hypoxia causes vascular endothelium release adenosine.

Adenosine acts A1 receptors on endothelial cells that are coupled to KATP channels, and cause synthesis NO, which then acts on vascular smooth muscle to cause vasodilatation

*Extrinsic: control peripheral blood flow- sympathetic nervous system effect on vascular smooth muscle
*Intrinsic: autoregulation /myogenic/metabolic/endothelium
*Dual control important vascular adjustments
*Direct blood flow to areas where it is most needed