Elevated plasma noradrenaline in response to beta-adrenoceptor stimulation in man

Abstract

1 Dose-dependent increments of plasma noradrenaline were observed during graded infusions of (±)isoprenaline (3.5-35 ng kg^-1 min^-1 i.v.) in seven normal subjects and in ten subjects with borderline hypertension. At the highest dose of isoprenaline, noradrenaline rose by 166 ± 16 pg/ml in normals and by 169 ± 34 pg/ml in hypertensives (mean ± s.e. mean).

2 In the subjects with borderline hypertension isoprenaline infusions were repeated after 7 days of treatment with (±)propranolol (320 mg/day, divided into 4 doses) and subsequently after 7 days of treatment with (±)atenolol (100 mg/day) 2-3 h after the morning dose of β-adrenoceptor blocker. The dose-response curve for plasma noradrenaline was shifted to higher doses of isoprenaline by a factor of 4 by atenolol and the heart rate response was similarly shifted. The heart rate response was shifted by a factor of 16 by propranolol, but plasma noradrenaline did not change after isoprenaline under propranolol treatment, even when isoprenaline was given at doses high enough to induce increments of heart rate similar to those without β-adrenoceptor blocker treatment.

3 In the subjects with borderline hypertension mean and diastolic intra-arterial pressures fell at the highest dose of isoprenaline by 9 ± 2 and 13 ± 2 mm Hg respectively. These effects were antagonized by propranolol and not by atenolol.

4 The observed rise in plasma noradrenaline after isoprenaline might have been caused by baro-reflex-stimulation of central sympathetic outflow. The isoprenaline-induced decrease in mean arterial pressure, however, was small. Moreover pulse pressure rose and this tends to suppress rather than stimulate baroreflex-mediated sympathetic activity. Activation of presynaptic β-adrenoceptors, allegedly of the β₂-subtype, is known to facilitate noradrenaline release upon nerve stimulation of isolated tissues. Our results lend support to the hypothesis that such a facilitatory mechanism is also operative in intact man.