Ses 5 ANS and Hypertension CVS

Question 1

detail the neurotransmitters and receptors involved in the
autonomic nervous system

Answer 1

Preganglionic neurones of both divisions release Ach which acts on nicotine Ach receptors on postganglionic cell.

In sympathetic post ganglionic - usually releases noradrenaline which binds to adrenergic receptors.

In para post ganglion Ach released but binds to muscarinic ACh receptors.

Question 2

ANS what does it control notion for examples

Answer 2

– smooth muscle (vascular and visceral)
– exocrine secretion
– rate and force of contraction in the heart

Question 3

Adrenoreceptors and muscarinic receptors

Answer 3

A = G protein-coupled receptors
• α-adrenoreceptors
– α1-(Gq), α2-(Gi)
• β-adrenoreceptors (Gs)
– β1, β2, also β3

M = G protein-coupled receptors
M1(Gq), M2(Gi), M3(Gq)

Both
• Different tissues can have different subtypes
– Allows for diversity of action
– Selectivity of drug action

Question 4

ANS control of heart rate and force of contraction - nerve, where does it act, receptors

Answer 4

Para input to heart:
10th cranial nerve - vagus
Synapse with postganglionic cells on epicardial surface or within
walls of heart predominantly at SA and AV node.
Acts on M2-receptors:
Dec HR/ -ve chronotropic effect
Dec AV node conduction velocity

Sympa
Innervate SA node, AV node and myocardium - release NA
β1 adrenoreceptors
Inc HR and force of contraction (+ve inotropic effect)

Question 5

explain the cellular mechanisms by which the ANS controls heart rate

Answer 5

Sympa
G-protein coupled receptors (Gs which stimulates adenylate cyclase) - beta 1
Increase cAMP which inc speeds up funny current which speeds up pacemaker potential

Para
G-protein coupled receptors (Gi which inhibits adenylate cyclase)
Increase K+ conductance (dec depolarisation) and decrease cAMP

Question 6

explain the cellular mechanisms by which the ANS controls force of contraction in the heart

Answer 6

noradrenaline increase force of contraction
NA acting on β1 receptors in
myocardium causes an increase
in cAMP → activates PKA

1. Phosphorylation of Ca2+ channels increases Ca2+ entry during the plateau of the AP
2. Increased uptake of Ca2+ in
   sarcoplasmic reticulum
   • More Ca2+ available for release from stores

Leads to increased force of
contraction

Question 7

describe the mechanisms which control contraction of vascular
smooth muscle cells

Answer 7

Had basal vasomotor tone

most vessels receive sympathetic innervation - mostly α1-adrenoreceptors - NA from SNS - vasoconstriction.
Stimulates IP3 production
Calcium-calmodulin complex activates MLCK which phosphorylates the regulatory myosin light chain
Plus DAG inhibiting myosin light chain phosphatase
Increase in [Ca2+]intracellular from stores and influx of extracellular Ca2+ → contraction of smooth muscle
Gq coupled - leads to inositol trisphosphate (IP3) and
diacyl glycerol (DAG) production

At high levels adrenaline binds to alpha 1

coronary and skeletal muscle vasculature also have β2-receptors - adrenaline has a higher affinity for them at normal levels - causes vasodilation- Increases cAMP → PKA → opens potassium channels + inhibits MLCK→ relaxation of smooth muscle
Gs coupled

Question 8

Role of local metabolites in vsm

Answer 8

Active tissue produces more metabolites
Local increases in metabolites have a strong vasodilator effect
ensuring adequate perfusion of skeletal and coronary muscle

Question 9

explain the role of the autonomic nervous system in controlling
peripheral resistance

Answer 9

Inhibition of SNS to heart and vessels Activation of PNS to heart in response to increase arterial BP

Question 10

describe the baroreceptor reflex

Answer 10

Nerve endings in the carotid sinus and aortic arch are sensitive to stretch.
Increased arterial pressure stretches these receptors.
Message sent to medulla
Neg effect on SNS - bradycardia and vasodilation to lower BP

The baroreceptor reflex is important for maintaining arterial BP over short term.
HOWEVER Baroreceptors can re-set to higher levels with persistent increases in blood
pressure.

Question 11

define the stages of hypertension

Answer 11

Stage 1 hypertension ≥ 140/90 mmHg

Stage 2 hypertension ≥160/100 mmHg

Severe hypertension ≥ 180 systolic or ≥ 110 diastolic

Question 12

explain the impact of hypertension on organs and tissues in the body

Answer 12

Damaging effects on heart and vasculature
Potentially leading to heart failure, MI, stroke, renal failure and retinopathy
Brain, eyes, heart, kidneys, arteries

Question 13

Medium and longer term control of blood pressure
What is main part of their response
4

Answer 13

Directed at controlling sodium balance and thus extracellular fluid volume

1. Renin-angiotensin-aldosterone system
2. Sympathetic nervous system 3. Antidiuretic hormone (ADH)
3. Atrial natriuretic peptide (ANP)

Question 14

RAAS

Answer 14

Reduced NaCl delivery to macula dense of distal tubule
Reduced perfusion pressure in the kidney causes the release
of renin detected by baroreceptors in afferent arteriole
Sympathetic stimulation to juxtaglomerular apparatus to inc renin

Converts angiotensinogen to angiotensin I
ACE(angiotensin converting enzyme - also breaks down bradykinin which is a vasodilator) converts it to angiotensin II
This causes vasoconstriction, stimulates Na+ absorption in kidneys, stimulates aldosterone, inc ADH release. Main actions via AT1 receptor.

aldosterone:
• acts on principal cells of collecting ducts
• stimulates Na+ and therefore water reabsorption
• activates apical Na+ channel (ENaC, Epithelial Na Channel)
and apical K+ channel
• also increases basolateral Na+ extrusion via Na/K/ATPase

ACE inhibitors used to stop this process and has hypotensive effects.

Question 15

Sympathetic nervous system

Answer 15

reduce renal blood flow
– Vasoconstriction of arterioles
– Decrease GFR – decrease Na+ excretion

• Activates apical Na/H-exchanger and basolateral Na/K
ATPase in PCT

• Stimulates renin release from JG cells

Question 16

Antidiuretic Hormone (ADH)

Answer 16

Increases water reabsorption in distal nephron (AQP2)

stimulates Na+ reabsorption
– Acts on thick ascending limb
– stimulates apical Na/K/Cl co-transporter

Causes vasoconstriction

Question 17

Natriuretic peptides

Answer 17

promotes Na+ excretion along nephron - Causes natriuresis (loss of sodium into urine)

• synthesised and stored in atrial myocytes
• released from atrial cells in response to stretch
– reduced filling of the heart – less stretch – less ANP released

Causes vasodilation of the afferent arteriole - Increased blood flow increases GFR

Question 18

2 other molecules that involve in BP

Answer 18

Prostaglandins - Locally acting prostaglandins (mainly PGE2) enhance glomerular filtration and reduce Na+ reabsorption

Dopamine - reduces reabsorption of NaCl
– Inhibits NH exchanger and Na/K ATPase in principal cells of PCT

Question 19

Secondary hypertension adrenal

Answer 19

Conn’s syndrome – aldosterone secreting adenoma - hypertension and hypokalaemia
• Cushing’s syndrome – excess secretion of glucocorticoid cortisol – at high concentration acts on aldosterone receptors
• Tumour of the adrenal medulla – phaeochromocytoma – secretes catecholamines

Question 20

Secondary hypertension: Renovascular disease

Answer 20

Occlusion of the renal artery (renal artery stenosis) causes a fall in perfusion pressure in that kidney
• Decreased perfusion pressure leads to increased renin production

Question 21

Treating hypertension notion

Answer 21

First = lifestyle
Eg exercise, diet, less salt and alcohol

Meds
Raas
ACE inhibitors eg captopril
Angiotensin Receptor Blockers (ARBs) eg Losartan
Vasodilators
L-type Ca channel blockers (eg Verapamil) – reduce Ca2+ entry to vascular smooth muscle cells
α1 receptor blockers (eg Doxazosin) - can cause postural hypotension
Diuretics
Beta blockers - reduce SNS - used when previous MI