Noradrenaline kinetics and coronary haemodynamics during acute beta 1-adrenoceptor blockade in man

1. To investigate the effects of acute beta 1-adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 micrograms min-1 kg-1) in 10 patients undergoing diagnostic cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 7 days. 2. Coronary haemodynamics were measured in these 10 patients plus two others. Compared with saline placebo, metoprolol administration was associated with decreases in heart rate (68 +/- 2 to 59 +/- 3 beats/min, P < 0.001) and coronary sinus blood flow (86 +/- 8 to 68 +/- 6 ml/min, P < 0.001) and an increase in calculated coronary vascular resistance (1.42 +/- 0.19 to 1.75 +/- 0.22 mmHg min ml-1, P < 0.001). Arterial and femoral venous noradrenaline concentrations, whole-body noradrenaline clearance and whole-body noradrenaline spillover to arterial plasma did not change. In contrast, cardiac noradrenaline spillover (33.7 +/- 5.1 to 20.2 +/- 4.3 pmol/min, P < 0.05) and cardiac noradrenaline clearance (31 +/- 3 to 23 +/- 3 ml/min, P < 0.001) were significantly decreased during metoprolol administration. 3. These results may be explained by inhibition of pre-junctional facilitatory beta-adrenoceptors, which we hypothesize may be predominantly of the beta 1-subtype in the heart and of the beta 2-subtype in the periphery.