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

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

4. 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

5. 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

6. 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)

7. 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

8.  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

9. 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

10. 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