Transcript lab# 7.ppt
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 α1 Vasoconstriction NA≥A>ISO - Phentolamine - Prazocin α2 Inhibition of NT release A>NA>ISO - Phentolamine - Yohimbine β1 Increase CO ISO>A>NA - Propranolol - Atenolol β2 Vasodilatation 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) Reflex - It has mild β1 stimulant effect → ↑CO (↑systolic BP) 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 ↓ NA ↓ Phentolamine Adrenaline 1mg/kg NA 1mcg/kg Adrenaline Isoprenaline ↓ Ach Atropine 0.5 mcg/ kg Ach 0.5mcg/kg Ach 100 mcg/ kg