1. 313 PHL Lab # 6 Effect of different drugs on the blood pressure of anaesthetized rabbit

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

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 Receptor TypeMain ActionAgonistAntagonist α1α1 VasoconstrictionNA≥A>ISO- Phentolamine - Prazocin α2α2 Inhibition of NT release A>NA>ISO- Phentolamine - Yohimbine β1β1 Increase COISO>A>NA- Propranolol - Atenolol β2β2 VasodilatationISO>A>NA -Propranolol - butoxamine

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. 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)

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.

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 Adrenaline 1mg/kg NA 1mcg/kg Isoprenaline ↓ Phentolamine Adrenaline ↓ NA Ach 0.5mcg/kg ↓ Atropine Ach 0.5 mcg/ kg Ach 100 mcg/ kg