Beta-adrenergic receptor-mediated release of norepinephrine in the human forearm.
Because of difficulties in separating the systemic from local effect, the role of presynaptic beta 2-adrenergic receptors in facilitating the neural release of norepinephrine has not been defined previously in humans in vivo. To determine whether stimulation of presynaptic beta-receptors alters local release of norepinephrine, we examined the effects on norepinephrine kinetics of 60 and 400 ng/min intra-arterial isoproterenol in seven healthy male volunteers. Isoproterenol, 60 ng/min, increased forearm norepinephrine spill-over sixfold from a baseline spillover of 0.45 +/- 0.08 to 2.89 +/- 0.69 ng/min (p < 0.01), whereas 400 ng/min isoproterenol increased forearm norepinephrine spillover to 13.25 +/- 2.49 ng/min (p < 0.005), a 29-fold increase above baseline. Coinfusion of 20 to 40 micrograms/min propranolol with 400 ng/min isoproterenol in four subjects significantly attenuated the isoproterenol-induced increase in local norepinephrine spillover to 2.09 +/- 0.92 ng/min (p < 0.05 versus 400 ng/min isoproterenol). This study shows that presynaptic beta-adrenergic receptors facilitate local release of norepinephrine in vivo in humans.
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602.
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D000328:Adult; D001158:Arteries / Q000294:innervation; D001916:Brachial Artery; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013569:Synapses / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine