Blood pressure and norepinephrine spillover during propranolol infusion in humans

To determine whether a reflex increase of sympathetic nervous system activity contributes to maintenance of blood pressure during acute beta-adrenergic blockade, we measured plasma norepinephrine levels and norepinephrine kinetics during propranolol administration. During a 90-min infusion of propranolol (10 mg iv + 80 micrograms/min) in 12 normal subjects, heart rate fell from 56 +/- 2 to 49 +/- 2 (SE) beats/min (P less than 0.001), but there was no fall in mean arterial blood pressure (84 +/- 3 mmHg before and 86 +/- 3 mmHg after propranolol). Arterial plasma norepinephrine levels rose from 183 +/- 20 to 250 +/- 29 pg/ml during propranolol (P less than 0.001), suggesting increased sympathetic vasoconstrictor tone. However, isotope dilution studies using tritiated norepinephrine infusion showed that arterial plasma levels of tritiated norepinephrine rose from 743 +/- 78 to 1,002 +/- 101 dpm/ml during propranolol (P less than 0.001), indicating a reduction in the rate of norepinephrine clearance from plasma. The calculated fall in clearance from 1.90 +/- 0.13 to 1.42 +/- 0.11 1/min (P less than 0.001) entirely accounted for the rise in plasma norepinephrine, since the calculated rate of norepinephrine spillover into plasma remained at the base-line level of 340 +/- 40 ng/min during propranolol. In control studies on four subjects, arterial plasma norepinephrine levels and norepinephrine kinetics did not change from base line during the control period. We conclude that maintenance of blood pressure during propranolol infusion is not due to a reflex generalized increase of sympathetic vasoconstrictor tone.