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313 PHL Lab # 7

313 PHL Lab # 7 Effect of different drugs on the blood pressure of anaesthetized rabbit. Normal Regulation of blood pressure (BP) :. Systolic BP. Diastolic BP. BP = CO x PR. Principle :. Rabbit BP is measured from carotid artery of anaesthetized

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313 PHL Lab # 7

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  1. 313 PHL Lab # 7 Effect of different drugs on the blood pressure of anaesthetized rabbit

  2. Normal Regulation of blood pressure (BP) : Systolic BP Diastolic BP BP = CO x PR

  3. 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 .

  4. Autonomic nervous system and BP: Sympathetic nervous system : - Increases BP . - Increases heart rate . Parasympathetic nervous system : - Decreases BP . - Decreases heart rate .

  5. Sympathetic nervous system: Receptors involved in BP regulation

  6. 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

  7. Sympathomimetics; cont. Reflex bradycardia (vagal nerve stimulation) 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)

  8. 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

  9. Sympathomimetics; cont. 4- Clonidine: -α2 agonist with mild α1effect used as antihypertensive agent . - Should be taken orally not IV (Why) .

  10. 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 .

  11. 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 .

  12. Effect of different drugs on the blood pressure of anaesthetized rabbit ↓ NA ↓ Atropine Ach 0.5 mcg/kg ↓ Phentolamine Ach 100 mcg/kg Ach 0.5mcg/kg Adrenaline 1mg/kg NA 1mcg/kg Adrenaline Isoprenaline

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