Department of PharmacologyYun-Bi Lu, San-Hua Fang, Wei-Wei Hu

yunbi@zju.edu.cnfshfbzxhq@zju.edu.cn

huww@zju.edu.cn

Effects of adrenergic receptor Effects of adrenergic receptor agonists / antagonists on agonists / antagonists on arterial blood pressure in rabbitarterial blood pressure in rabbit

[Objectives]

To observe the pharmacological effects of adrenergic agonists on regulation of arterial blood pressure in rabbit.

To demonstrate and analyze the underlying mechanisms of adrenergic agonists actions by using adrenergic antagonists.

[Principle]

vasodilation(skeletal muscle vasculature)

enhancement of heart rate, contractility and conduction velocity

inhibition of norepinephrinerelease

Vasoconstriction(arterioles, veins)

Effects

Postsynaptic,blood vessels

Postsynaptic, heart

PresynapticPostsynaptic, Smooth muscular cells of blood vessels

Distribution

β2β1α2α1Receptor type

[Principle]

antagonistβ1, β2propranololantagonistα1, α2phentolamine

agonistβ1, β2Isoprenaline(isoproterenol)

agonistα1, α2 (β1)Noradrenaline(norepinephrine)

agonistα1, α2, β1, β2Adrenaline(epinephrine)

EffectReceptor specificityDrug

Adrenoceptors

Effects of Effects of catecholaminescatecholamines（（therapeutic dosestherapeutic doses））

Predominant Effects:Predominant Effects:NE :NE : αα effects effects & & veryvery weakweak ββ11 effectseffectsEPI :EPI : αα effects (higher concentrations)effects (higher concentrations) ββ effects (lower concentrations) effects (lower concentrations) ISO: ISO: ββ11 and and ββ 2 2 effectseffects

Isoprenaline( )

Noradrenaline( )

Adrenaline ( )

Phentolamine( )

Isoprenaline( )

Noradrenaline( )

Adrenaline ( )

Control

Heart rate (bpm)

Pulse pressure (mmHg)

SP/DP[Systolic blood

pressure /Diastolic blood pressure](mmHg)

Treatment 2 (dose)

Treatment 1 (dose)

control control control

control

The underlying action mechanism of adrenaline

ββ1:1: contractility contractility ↑↑HR HR ↑↑

αα11：：vasoconstriction vasoconstriction (skin, mucous, viscera), (skin, mucous, viscera),

ββ22：：vasodilatation of skeletal vasodilatation of skeletal muscles and coronary vesselsmuscles and coronary vessels

cardiac output cardiac output ↑↑Peripheral resistancePeripheral resistance--↓↓

Systolic BP Systolic BP ↑↑Diastolic BP Diastolic BP ↓↓(slightly)(slightly)Pulse pressurePulse pressure ↑↑

The underlying action mechanism of noradrenaline

αα11：：vasoconstriction (skin, renal, brain, vasoconstriction (skin, renal, brain, hepatic, mesenteric, hepatic, mesenteric, etcetc.).)

αα22：：inhibiting NE releaseinhibiting NE releaseββ1: 1: weak directly cardiac stimulatesweak directly cardiac stimulates

cardiac output cardiac output ↑↑ (slightly) (slightly) Peripheral resistancePeripheral resistance ↑↑

Systolic BP Systolic BP ↑↑Diastolic BP Diastolic BP --pulse pressure pulse pressure ↑↑

cardiaccardiac inhibition inhibition viaviareflexreflex ((baroreceptorbaroreceptor))

Heart rate Heart rate ↓↓

The underlying action mechanism of isoproterenol

ββ1:1: contractility contractility ↑↑ HR HR ↑↑ββ2 :2 : dilatation of skeletal muscles dilatation of skeletal muscles and coronary vesselsand coronary vessels

cardiac output cardiac output ↑↑Peripheral resistancePeripheral resistance ↓↓

Systolic BP Systolic BP ↑↑Diastolic BP Diastolic BP ↓↓pulse pressure pulse pressure ↓↓

BP

αα antagonistantagonistX drugX drug X drugX drug

Experiment Report

SubjectObjectivesMaterials and methods:ResultsDiscussionConclusion