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 o f beta-adrenoceptor responses occurs after exposure to agonist. Tachyp hylaxis to a beta-adrenoceptor agonist would represent a potentially i mportant mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproteren ol on forearm blood flow and presynaptic beta-adrenoceptor-mediated no repinephrine release were determined in eight healthy volunteers. Intr a-arterial isoproterenol at 400 ng/min resulted in a significant incre ase in forearm blood flow in all eight subjects at all time points, wi th no evidence of tachyphylaxis. In fact, forearm blood flow after 4 h ours of the isoproterenol infusion (22.8+/-3.3 mL/100 mL per minute) w as significantly greater than after 7 minutes (14.6+/-2.8 mL/100 mL pe r minute), 15 minutes (15.4+/-2.4 mL/100 mL per minute), and 30 minute s (17.4+/-3.0 mL/100 mL per minute) of the infusion (P<.05). Similarly , presynaptic beta-adrenoceptor responses showed no evidence of tachyp hylaxis, so forearm norepinephrine spillover values after 7 minutes (6 .6+/-0.94 ng/min), 15 minutes (7.6+/-1.5 ng/min), and 4 hours (8.8+/-1 .1 ng/min) of isoproterenol infusion were increased and similar. Minim al systemic effects were observed, and there was no evidence of tolera nce, there being no difference in heart rate after 7 minutes (70.7+/-2 .7 beats per minute) and 4 hours (72.2+/-3.6 beats per minute) of isop roterenol infusion. Similarly, systemic norepinephrine spillover value s at 7 minutes (422.6+/-60.6 ng/min), 15 minutes (436.3+/-48.7 ng/min) , and 240 minutes (491.4+/-52.9 ng/min) all increased from a baseline value of 294+/-28.2 ng/min (P<.05) but were not significantly differen t from each other. Tachyphylaxis does not occur rapidly after exposure of forearm vascular smooth muscle to the beta-adrenoceptor agonist is oproterenol and is unlikely to play a major role in the rapid regulati on of vascular response to a beta-adrenoceptor agonist.