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 beta-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a beta-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 beta-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 < .05). Similarly, presynaptic beta-adrenoceptor responses showed no evidence of tachyphylaxis, 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. Minimal systemic effects were observed, and there was no evidence of tolerance, 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 isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Stein
C M
CM
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Nelson
R
R
Deegan
R
R
He
H
H
Inagami
T
T
Frazer
M
M
Badr
K F
KF
Wood
M
M
Wood
A J
AJ
D000328:Adult; D000804:Angiotensin II / Q000096:biosynthesis; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013618:Tachyphylaxis; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D007545:Isoproterenol