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 alpha 2-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 alpha 2-blocker yohimbine (Yoh, 125 micrograms/kg bolus, 1 microgram.kg-1.min-1 infusion) in seven normal volunteers. Yoh administration increased mean arterial pressure by 16% (P less than 0.005), heart rate by 8% (P less than 0.05), and forearm vascular resistance by 67% (P less than 0.05). MSNA was increased by 73% (P less than 0.05), NE spillover into arterial blood by 125% (P less than 0.05), and forearm NE spillover (FSO) by 337% (P less than 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 alpha 2-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.
Grossman
E
E
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Rea
R F
RF
Hoffman
A
A
Goldstein
D S
DS
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000648:ultrastructure; D009638:Norepinephrine / Q000097:blood*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014294:Trimethaphan / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D014294:Trimethaphan; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine