A healthy volunteer receives a continuous intravenous infusion of norepinephrine. Compared to baseline, the expected hemodynamic response is an increase in blood pressure and a decrease in heart rate. The decrease in heart rate is primarily due to:

• A Direct stimulation of muscarinic receptors in the sinoatrial node by norepinephrine
• B Stimulation of presynaptic alpha-2 receptors, which inhibits further norepinephrine release and slows the heart
• C Baroreceptor-mediated reflex activation of the parasympathetic nervous system, overriding the direct beta-1 chronotropic effect ✓
• D Direct stimulation of alpha-1 receptors in the atrioventricular node, slowing conduction

Explanation

Norepinephrine directly stimulates cardiac beta-1 receptors, which would normally increase heart rate. However, its potent alpha-1 mediated vasoconstriction significantly raises mean arterial pressure. This activates the arterial baroreceptors, leading to a reflex increase in parasympathetic outflow and a decrease in sympathetic outflow. This baroreflex overrides the direct cardiac beta-1 effect, resulting in a net decrease in heart rate. Distractor B is incorrect because presynaptic alpha-2 stimulation inhibits endogenous norepinephrine release from nerve terminals, but the infused drug acts directly on vascular and cardiac receptors.

Reference: Ganong's Review of Medical Physiology, 26th ed.

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