An intravenous infusion of epinephrine raises blood pressure in a healthy volunteer. When the infusion is repeated after pretreatment with phentolamine, the blood pressure falls below baseline. What accounts for this reversal?

• A Phentolamine blocks epinephrine-induced histamine release
• B Unmasked beta-2 mediated vasodilation once alpha-1 vasoconstriction is blocked ✓
• C Phentolamine directly stimulates beta-1 receptors in the heart
• D Epinephrine switches to acting as a presynaptic alpha-2 antagonist

Explanation

This is classical epinephrine reversal. Epinephrine activates both alpha-1 receptors causing vasoconstriction and beta-2 receptors causing skeletal muscle vasodilation. Normally the alpha effect dominates and pressure rises. Phentolamine removes the alpha component, leaving beta-2 vasodilation unopposed, so pressure falls while heart rate rises further. Phentolamine has no intrinsic beta-agonist activity and does not alter histamine release or presynaptic signalling in this way.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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