Learning Objective

Explain the receptor profile, dose-dependent effects, cardiovascular responses, and unique β2-mediated actions of norepinephrine and epinephrine, and describe how epinephrine reversal distinguishes high-dose epinephrine from norepinephrine.

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Norepinephrine (NE): Receptor profile: α1, α2, β1

Physiologic effects

• α1 → ↑ systemic vascular resistance → ↑ systolic & diastolic BP
• β1 → ↑ contractility & ↑ HR (direct effect)
  But reflex bradycardia dominates due to ↑ BP.

Hemodynamic pattern

• ↑↑ BP
• ↓ HR (reflex)
• ↑ CO only mildly

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Epinephrine (Epi): Receptor profile: α1, α2, β1, β2

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Low-dose Epi (β > α)

• β1 → ↑ HR, ↑ contractility
• β2 → vasodilation → ↓ diastolic BP
• Pulse pressure widens

Net: ↑↑ HR, ↑ systolic BP, ↓ diastolic BP

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Activity

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Medium-dose Epi

• β is still dominant, but α1 begins acting

• HR ↑↑
• Systolic BP ↑, diastolic ≈ normal or slightly ↓

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High-dose Epi (α > β)

• Now resembles norepinephrine

• α1 → vasoconstriction → ↑ BP
• Mixed HR effect (β1 ↑ vs reflex ↓)

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Activity

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β2-Specific Effects of Epinephrine

Smooth muscle relaxation

• Bronchodilation
• Uterine relaxation
• Vascular dilation in skeletal muscle

Metabolic

• ↑ glycogenolysis (liver, muscle)
• ↑ gluconeogenesis
• ↑ lipolysis
• ↑ lactate

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Epinephrine Reversal

Differentiates high-dose Epi from NE

What happens?

• High-dose Epi → hypertension (α1 vasoconstriction)
• Give α1 blocker (e.g., phentolamine) → BP falls to hypotension

Why?

• Loss of α1 vasoconstriction
• Unopposed β2 vasodilation → ↓↓ BP

Key point

• NE cannot show epinephrine reversal (no significant β2 activity)

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Quick Comparison Table