313 PHL

Lab # 7

Effect of different drugs on the blood pressure of anaesthetized rabbit

Normal Regulation of blood pressure (BP) :

BP = CO x PR

Systolic BP Diastolic BP

Principle :

• Rabbit BP is measured from carotid artery of anaesthetized

rabbit and drugs are injected into jugular vein .

• Rabbit BP is measured from central ear artery of conscious rabbit and drugs are injected into marginal ear vein .

Autonomic nervous system and BP:

Sympathetic nervous system : - Increases BP .

- Increases heart rate .

Parasympathetic nervous system : - Decreases BP .

- Decreases heart rate .

Sympathetic nervous system: Receptors involved in BP regulation

Receptor Type Main Action Agonist Antagonist

α1Vasoconstriction NA≥A>ISO - Phentolamine

- Prazocin

α2Inhibition of NT release

A>NA>ISO - Phentolamine

- Yohimbine

β1Increase CO ISO>A>NA - Propranolol

- Atenolol

β2Vasodilatation ISO>A>NA -Propranolol

- butoxamine

Drugs affecting BP:

Sympathomimetics :

1- Adrenaline (3 mcg/kg)MOA:

- On β1 R (in the heart)→st. Gs protein→↑Adenylyl cyclase (AC)→↑cAMP→↑calcium influx→↑HR, force of contraction (+ve inotropic & chronotropic) → ↑ systolic BP.

- On α1 R (in BV) → ++ PLC (IP3 & DAG)→↑calcium influx →vasoconstriction →↑ PR→ ↑ diastolic BP.

- On β2 R (in BV) →st. Gs protein → ↑ cAMP-dependent protein kinase → phosphorylates myosin light-chain kinase → relaxation of smooth muscles → HYPOTENSION

Net effect: Biphasic change in BP

Sympathomimetics; cont.

2- Noradrenaline (1 mcg/kg)

MOA:

- It acts mainly on α1 R → VC & ↑PR (↑ diastolic BP)

- It has mild β1 stimulant effect → ↑CO (↑systolic BP)

Reflex bradycardia(vagal nerve stimulation)

Sympathomimetics; cont.

3- Isoprenaline :

- It is non-selective β agonist .

- It stimulates β1 in the heart →↑CO (weak effect) → ↑ systolic BP .

- It stimulate β2 in the BV → ↓ PR (predominant effect) → ↓diastolic BP .

NET EFFECT: ↓ BP

Sympathomimetics; cont.

4- Clonidine:

- α2 agonist with mild α1effect used as antihypertensive agent .

- Should be taken orally not IV (Why) .

α receptors blockers :

Selective α 1 blockers:

e.g. prazosin, doxazocin .

Non-selective(α 1 & α 2) blockers :

e.g. Phentolamine (causes hypotension) .

Selective α 2 blocker :

e.g. Yohimbine (it increases the BP) .

N.B. α blockers reverse the action of Adrenaline & abolish the effect of Noradrenaline .

Parasympathomimetic :

1- Acetylcholine :

Low dose (0.5 mcg/kg) acts on endothelial cells of BV to release NO causing vasodilatation & ↓ PVR & BP .

Blocker: atropine .

N.B. high dose of Ach (50mcg/kg) increase the BP due to:

1- Stimulation of sympathetic ganglia→↑ NA release from postganglionic fibers .

2- Stimulation of adrenal medulla →↑ A & NA release .

Effect of different drugs on the blood pressure of anaesthetized rabbit

Adrenaline1mg/kg

NA1mcg/kg Isoprenaline

↓Phentolamine

Adrenaline

↓NA

Ach0.5mcg/kg

↓

Atropine Ach0.5mcg/kg

Ach100mcg/kg