1. Effect of different drugs on blood pressure Lab # 7

2. Outlines Explain the normal regulation of blood pressure Explain the normal regulation of blood pressure Study the effect of certain drugs on the BP Study the effect of certain drugs on the BP Explain the types of receptors & NT involved in BP regulation Explain the types of receptors & NT involved in BP regulation

3. Normal Regulation of BP BP = CO x PVR Systolic BP Diastolic BP

4. Autonomic NS and BP Sympathetic NS Sympathetic NS - Increases BP - Increases BP - Increases heart rate - Increases heart rate Parasympathetic NS Parasympathetic NS - Decreases BP - Decreases BP - Decreases heart rate - Decreases heart rate

5. Sympathetic nervous system: Receptors involved in BP regulation Receptor Type Main Action AgonistAntagonist 1111VasoconstrictionNA>A>ISOPhentolaminePrazocin 2222 Inhibition of NT release A>NA>ISOPhentolamineYohimbine 1111 Increase CO ISO>NA>APropranololAtenolol 2222VasodilationISO>A>NAbutoxamine

6. Drugs affecting BP Sympathomimetics 1- Adrenaline (3 mcg/kg) MOA: - On  1 R (in the heart)→st. Gs protein→↑AC→↑cAMP→↑calcium→↑HR, force of contraction (+ve inotropic & chronotropic) → ↑ SYSTOLIC BP. - On  1 R (in BV) →st. Gs protein→↑AC→↑cAMP→↑calcium →vasoconstriction →↑ PVR→ ↑ DIASTOLIC BP. - On  2 R (in BV) →st. Gi protein→↑Guanylyl cyclase→↑cGMP→↓calcium & ↑K→ hyperpolarization → Vasodilatation → HYPOTENSION Net effect: Biphasic change in BP

7. Sympathomimetics; cont. 2- Noradrenaline (1 mcg/kg) MOA: - - It acts mainly on  1 R → VC & ↑PVR (↑ diastolic BP) - - It has mild  1 stimulant effect → ↑CO (↑systolic BP) - Sss Sss Reflex bradycardia (vagal nerve stimulation)

8. Sympathomimetics; cont. 3- Isoprenaline - - It is non-selective  agonist - - It stimulates  1 in the heart →↑CO (weak effect) &  2 in the BV →↓PVR (predominant effect) NET EFFECT: ↓ BP 4- Clonidine      agonist used as antihypertensive agent - Should not be taken IV

9.  receptors blockers   Selective     blockers: Ex. prazosin, doxazocin   Non-selective(       blockers Ex. Phentolamine (causes hypotension)   Selective    blocker Ex. Yohimbine (it increases the BP) N.B.  blockers reverse the action of adrenaline & abolish the effect of noradrenaline

10. Parasympathomimetic Example: -Low dose Ach (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

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