Tachyphylaxis of human forearm vascular responses does not occur rapidly after exposure to isoproterenol

In vitro and limited in vivo data suggest that rapid desensitization of β-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a β-adrenoceptor agonist would represent a potentially important mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproterenol on forearm blood flow and presynaptic β-adrenoceptor-mediated norepinephrine release were determined in eight healthy volunteers. Intra-arterial isoproterenol at 400 ng/min resulted in a significant increase in forearm blood flow in all eight subjects at all time points, with no evidence of tachyphylaxis. In fact, forearm blood flow after 4 hours of the isoproterenol infusion (22.8 ± 3.3 mL/100 mL per minute) was significantly greater than after 7 minutes (14.6 ± 2.8 mL/100 mL per minute), 15 minutes (15.4 ± 2.4 mL/100 mL, per minute), and 30 minutes (17.4 ± 3.0 mL/100 mL per minute) of the infusion (P