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To examine the existence of presynaptic β-adrenoceptors modulating forearm norepinephrine release in 31 healthy volunteers.The spillover rate of norepinephrine in forearm venous plasma and the total plasma appearance rate of norepinephrine in the forearm were estimated using intra-arterial infusion of [3H]-norepinephrine. Isoprenaline was infused intra-arterially to stimulate β-adrenoceptors, terbutaline to stimulate β2-adrenoceptors, propranolol to block β-adrenoceptors, metoprolol to block β1-adrenoceptors, isoprenaline combined with metoprolol to stimulate β2-adrenoceptors, epinephrine to stimulate α- and β-adrenoceptors, yohimbine to block α2-adrenoceptors and sodium nitroprusside to increase forearm blood flow directly.No systemic hemodynamic effects or changes in arterial plasma norepinephrine level were noted during the intra-arterial infusions. Metoprolol and propranolol decreased norepinephrine spillover and its rate of appearance in the forearm without affecting forearm blood flow. Isoprenaline and sodium nitroprusside increased and epinephrine decreased forearm norepinephrine spillover. Terbutaline increased forearm norepinephrine spillover and its rate of appearance in the forearm. Terbutaline increased the forearm rate of appearance and spillover of norepinephrine more than did sodium nitroprusside or isoprenaline at the same level of forearm blood flow. Infusion of isoprenaline failed to increase norepinephrine spillover or its forearm appearance rate more than would be expected from the increase in forearm blood flow. Administration of epinephrine increased spillover and forearm appearance rate of norepinephrine during intra-arterial infusion of yohimbine.The terbutaline, propranolol, metoprolol and yohimbine plus epinephrine results suggest that β-adrenoceptors enhance release of norepinephrine from vascular sympathetic nerve endings in humans.