Unchanged Peripheral Sympathetic Activity Following Withdrawal of Chronic Metoprolol Treatment. A Study of Noradrenaline Concentrations and Kinetics in Plasma

Noradrenaline plasma kinetics were assessed in 17 male patients, who had been treated with metoprolol 100-200 mg daily (n = 8) or placebo for 3 years after an acute myocardial infarction, before and 1 week after gradual withdrawal (during 1 week) of the study treatment. Endogenous noradrenaline concentrations in plasma were measured by high performance liquid chromatography. Noradrenaline spillover rate, plasma clearance and the t1/2 for the rapid removal from plasma were determined by radio-tracer methodology. During treatment the plasma noradrenaline concentrations and noradrenaline plasma kinetic variables were similar in the two groups. Venous plasma noradrenaline concentrations were more closely correlated to the spillover rates of noradrenaline to plasma than to the clearance of noradrenaline from plasma, but the spillover rates were correlated to the clearance rates. Following the withdrawal of metoprolol noradrenaline clearance from plasma increased slightly (by 18 +/- 5%, P less than 0.05), but the plasma concentrations and spillover rates of noradrenaline were unchanged. In the placebo group withdrawal did not result in any significant changes. Our results indicate that a generalised increase in sympathetic nerve activity is not the cause of so-called rebound phenomena following withdrawal of chronic beta-adrenoceptor blockade.