Yohimbine increases sympathetic nerve activity and norepinephrine spillover in normal volunteers

It has been difficult to examine clinically the physiological role of central and peripheral α₂-adrenoceptors in humans. We simultaneously measured directly recorded peroneal skeletal muscle sympathoneural activity (MSNA) and the rate of appearance (spillover) of norepinephrine (NE) in forearm venous and arterial plasma before and at 15 min during intravenous administration of the α₂-blocker yohimbine (Yoh, 125 μg/kg bolus, 1 μg·kg^-1·min^-1 infusion) in seven normal volunteers. Yoh administration increased mean arterial pressure by 16% (P < 0.005), heart rate by 8% (P < 0.05), and forearm vascular resistance by 67% (P < 0.05). MSNA was increased by 73% (P < 0.05), NE spillover into arterial blood by 125% (P < 0.05), and forearm NE spillover (FSO) by 337% (P < 0.005). Ganglion blockade by trimethaphan during Yoh infusion decreased MSNA to below detection limits and reversed Yoh-induced increases in arterial concentrations of NE and epinephrine. The results demonstrate that Yoh administration increases sympathoadrenal outflow. Because the mean increase of FSO was much larger than that of MSNA, the results suggest that α₂-adrenoceptors on sympathetic nerve endings modulate the neuronal release of NE for a given amount of sympathetic nerve traffic in humans; this effect seems prominent in the human limb.