Epinephrine-induced enhancement of sympathetic activity in humans: inhibition by nonselective as well as beta 1-selective beta-adrenoceptor blockade.
To collect further evidence that epinephrine (EPI) facilitates norepinephrine (NE) release in humans, the effect of a low-dose intravenous (i.v.) infusion of EPI (20 ng kg-1/min) on arterial levels of NE and on local production of NE in the forearm was studied both before and during isometric exercise, cold provocation, head-up tilting, and mental stress in 10 subjects with borderline to mild hypertension. Studies were performed during placebo, during beta 1-selective beta-adrenoceptor blockade with atenolol, 50 mg once daily, and during nonselective beta-blockade with bopindolol, 1 mg once daily. Atenolol and bopindolol were administered for 1 week, 2 weeks apart, in a randomized double-blind cross-over design. During infusion of EPI, which increased plasma EPI levels to within the high physiologic range, resting levels of NE increased from 214 +/- 20 to 263 +/- 26 pg/ml (p less than 0.01) and resting NE forearm production increased from 296 +/- 48 to 529 +/- 98 pg 100 ml/min-1 (p less than 0.01). The enhancement of these two indices of sympathetic activity by EPI, observed during placebo, was abolished by bopindolol as well as by atenolol. The response of arterial NE, but not the response of forearm NE production, to three of the four stress tests was also enhanced (p less than 0.05) by EPI. This enhancement was also abolished by both beta-adrenoceptor antagonists. Our findings support the hypothesis that physiologic levels of EPI are capable of enhancing sympathetic activity in humans. This effect is mediated by beta-adrenoceptors and can be blocked not only by a nonselective but also by a beta 1-selective beta-adrenoceptor antagonist.
Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
A H
AH
van den Meiracker
A J
AJ
Man in 't Veld
F
F
Boomsma
P J
PJ
Blankestijn
M A
MA
Schalekamp
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001262:Atenolol / Q000494:pharmacology*; D003080:Cold Temperature; D004837:Epinephrine / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D005082:Physical Exertion; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013315:Stress, Psychological
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D010869:Pindolol; C036007:bopindolol; D009638:Norepinephrine; D004837:Epinephrine