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This study investigates the influence of different pharmacological agents on the blood pressure of anaesthetized rabbits. Blood pressure is recorded via the carotid artery as drugs are administered through the jugular vein. It highlights the roles of the autonomic nervous system, with the sympathetic system elevating blood pressure and heart rate, while the parasympathetic system decreases them. Key drugs examined include adrenaline, noradrenaline, isoprenaline, clonidine, and acetylcholine, detailing their mechanisms of action and subsequent effects on systolic and diastolic blood pressure.
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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 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
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. 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)
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 ↓ NA ↓ Atropine Ach 0.5 mcg/kg ↓ Phentolamine Ach 100 mcg/kg Ach 0.5mcg/kg Adrenaline 1mg/kg NA 1mcg/kg Adrenaline Isoprenaline