Blood pressure and norepinephrine spillover during propranolol infusion in humans

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Abstract
To determine whether a reflex increase of sympathetic nervous system activity contributes to maintenance of blood pressure during acute .beta.-adrenergic blockade, plasma norepinephrine levels and norepinephrine kinetics were measured during propranolol administration. During a 90 min infusion of propranolol (10 mg i.v. + 80 .mu.g/min) in 12 normal subjects, heart rate fell from 56 .+-. 2 to 49 .+-. 2 (SE) beats/min (P < 0.001), but there was no fall in mean arterial blood pressure (84 .+-. 3 mm Hg before and 86 .+-. 3 mm Hg after propranolol). Arterial plasma norepinephrine levels rose from 183 .+-. 20 to 250 .+-. 29 pg/ml during propranolol (P < 0.001), suggesting increased sympathetic vasoconstrictor tone. Isotope dilution studies using tritiated norepinephrine infusion showed that arterial plasma levels of tritiated norepinephrine rose from 743 .+-. 78 to 1002 .+-. 101 dpm/ml during propranolol (P < 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 l/min (P < 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 4 subjects, arterial plasma norepinephrine levels and norepinephrine kinetics did not change from base line during the control period. Apparently maintenance of blood pressure during propranolol infusion is not due to sympathetic vasoconstrictor tone.