Epinephrine-induced enhancement of sympathetic activity in humans: Inhibition by nonselective as well as β₁-selective β-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^-1min) 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 β¹-selective β-adrenoceptor blockade with atenolol, 50 mg once daily, and during nonselective β-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 < 0.01) and resting NE forearm production increased from 296 ± 48 to 529 ± 98 pg 100 ml/min^-1 (p < 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 < 0.05) by EPI. This enhancement was also abolished by both β-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 β-adrenoceptors and can be blocked not only by a nonselective but also by a β,-selectivev β-adrenoceptor antagonist.