Practical Blood Pressure[1]

8/3/2019 Practical Blood Pressure[1]

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Computer simulationexperiments of effect of

different autonomic drugs on

arterial blood pressure & heartrate of rats

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Arterial blood pressure(ABP)

ABP is directly proportional to cardiac

output (COP) & peripheral vascularresistance (PVR)

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COP= HR X SV

PVR depends mainly on diameterof small sized arterioles

ABP = COP X PVR


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1sT experiment: effect of different doses

of norepinephrine (NA) on HR & ABP

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Inject 2 , 4 & 8 nmol/kg of NA

Observation: increased ABP with minimal effect onHR, which increases only with high doses


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Explanation of effect of NE on ABP& HR:

NE acts mainly on 1 receptorsVSM contractionvasoconstriction (skin, mucous

memb., splanchnic area)PVR

With higher doses of NE, itactivates also cardiac 1

receptors some increase in the

heart rate 4


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Design an experiment to prove thesuggested explanation

Inject an alpha adrenoceptor blocker andtest the effect of NE on ABP & HR

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What is the effect of prazosin onABP and HR?

It is an alpha blocker it blocks 1adrenoceptors vasodilation (skin,mucous membrane, splanchnic area)PVRABP

ABP slight reflex tachycardia

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2nd experiment: effect of different dosesof epinephrine on HR & ABP

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Observation: ABP & HRThe ABP before returning to base line level

Inject 2 , 4 & 8 nmol/kg


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Explanation of effect of epinephrineon HR & ABP

Epinephrine stimulates1, 1, 2adrenoceptors Beta receptors are moresensitive to the effect of epinephrine

On heart: 1 activation +ve inotropic &chronotropic effectsCOP leading toincreased ABP

On BV :

- 2 activation induces vSMC relaxation[sk.m. vascular bed )PVR

- 1activation causes vSM contraction vasoconstriction (skin, mucousmemb., splanchnic area) PVR. 8


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Explanation of effect of epinephrineon HR & ABP

The net effect of these two opposingeffects (1 & 2) on vSMC is an in PVR.

At lower epinephrine concentrations,the effect on alpha receptorsdecreases, while the activity on 2receptors predominates leading todecrease PVR & lowering ABP beforereturning to base line level

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D i i d


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Design an experiment to demonstrate

the role of 1 receptors in the effect ofadrenaline on HR & ABP

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&atenololInjecttest the effect of epinephrine on HR & ABP

receptors by atenolol blocks the1blockingObservation:

effect of epinephrine on HR & decreases the effect on ABP


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beta receptors & then injectepinephrine?

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Epinephrine reversal: The pressor effect of epinephrine is

reversed due to 1 & 1 blockade, leaving the 2 vasodilatingeffect acting ABP.


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How to confirm the cause ofepinephrine reversal? Inject prazosin then propranolol instead of

atenolol followed by injection of adrenaline

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No epinephrine reversal since propranolol blocks notonly cardiac 1 receptorsbut also vascular 2 receptors


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Compare between the effect of epinephrine

and norepinphrine on HR & ABP

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:Observation

of epinephrine & NE:equimolar dosesIn

Only epinephrine increases HR

NE produces higher increase in ABP


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Explanation

NE acts mainly on alpha receptors withminimal effect on beta receptorsminimal increase in HR

Absence of2 dilating effect explainswhy the PVR and ABP is more bynorepinephrine.

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r


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r exper men : e ec o erendoses of isoprenaline (Beta agonist)

on HR & ABP

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:Observation Isoprenaline increases HR

Isoprenaline initially decreases ABP.

As HR reaches its maximum increase, ABP shows

minimal increase before returning to normal


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Explanation for the effect ofisoprenaline on HR & ABP

Isoprenaline activates mainly betaadrenoceptor

It activates cardiac 1 receptors leading toincrease in HR & force of contraction (whichincreases COP)

Activation of 2 receptorsVasodilatondecrease in PVR

The net effect of the two factors (COP & PVR) isa decrease in blood pressure initially.

However, when force of contraction is markedlyelevated, the increase of COP overcomes the

effect of decrease in PVR and thus ABP starts to16

es gn an exper men o prove e


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es gn an exper men o prove eexplanation for the effect of isoprenaline onHR & ABP

Step1: Inject 1 blocker & then injectisoprenaline

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Observation: atenolol abolishes the effect ofisoprenaline on HR

The initial ABP-lowering effect of isoprenaline is

maintained, while its pressor effect is abolished


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Step 2: inject propranolol to block 2 receptorsfollowed again by isoprenaline

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Observation: Propranolol blocks 1 & 2 receptorsthus abolishes the effect of isoprenaline on ABP

Design an experiment to prove the explanationfor the effect of isoprenaline on HR & ABP

4th i t ff t f


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4th experiment: effect ofphenylephrine on HR & ABP

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Observation:

Small dose phenylephrine leads to slight increase in ABPwith no effect on HR

High dose phenylephrine increases markedly ABP withdecrease in the HR

E l ti f th ff t f


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Explanation of the effect ofphenylephrine on ABP & HR

Phenylephrine is an alphaadrenoceptor agonist

Activation of 1 receptors VSM

contraction vasoconstriction( skin,mucous memb., splanchnic area)PVR

High dose of phenylephrine markedelevation of ABP reflex insympathetic activity. Parasympathetic

activity will take the upper handHR 20

Design an experiment to prove the


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Design an experiment to prove theexplanation of the effect ofphenylephrine on HR and ABP Inject an alpha blocker followed by

phenylephrine

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Observation: prazosin decreases or abolishes the effect

of phenylephrine on ABP & reflex bradycardia disappears

ow o prove a re ex ra ycar a s ue


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ow o prove a re ex ra ycar a s ueto relative increase in parasympatheticactivity

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Observation: decreased HR is abolished by atropine

despite of elevation of ABP

E l ti f th ff t f


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Explanation for the effect ofacetylcholine on HR and ABP

on heart: M2 activation - vechronotropic effect COP

on BV: endothelial cells M3 activation release of NO from vascularendothelial cells vSMC relaxationPVR

Decrease in heart rate & decrease inPVR lead to ABP

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5th i t Eff t f diff t


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5th experiment: Effect of differentdoses of acetylcholine on ABP and HR

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Observation:small doses of acetylcholine lower only ABP

Higher doses produce both in the HR & more significantlowerin of ABP

es gn an exper ment to prove t e


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es gn an exper ment to prove t eexplanation of the effect ofacetylcholine on HR & ABP

Inject atropine & then test the effect ofacetylcholine

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Design an experiment to show


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Design an experiment to showacetylcholine reversal1. Inject a test dose of acetylcholine2. Inject atropine3. Inject the same dose of acetylcholine4. Inject a dose of acetylcholine which is 10

times the test dose

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mechanism of action of

neostigmine Inject a test dose of acetylcholine Inject neostigmine

Inject the test dose of acetylcholine

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Observation: Neostigmine increases the ABP- loweringeffect of acetylcholine & augments its effect on HR

Explanation for acetylcholine


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Explanation for acetylcholinereversal

Atropine injectionA parasympatholyticblocksmuscarinic receptors. It blocks the effect ofsmall dose of Ach.

Ach injection [big dose]Stimulates nicotinic

receptorsN

Nafter muscarinic receptors havebeen blocked by atropine Rise in ABP

Due to activation of NN at : Adrenal medulla release epinephrine BP

Autonomic ganglia release of catecholamines frompost-synaptic adrenergic nerve endings [sympatheticpredominance] BP

The BP by Ach [big dose] after muscarinic

receptor block [by atropine]Ach reversal 28

What is the effect of propranolol on


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What is the effect of propranolol onABP and HR?

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Practical Blood Pressure[1]

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