Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension

Abstract

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagonist of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metoprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 ± 3.8 (SEM)/10 ± 2.1 mm Hg in the lying position and 23 ± 4.419 ± 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p < 0.05) and decrease in exercise tachycardia (r = 0.65, p < 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mglkg. Metoprolol decreased PRA by 67 ± 1.9 and 71 ± 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p < 0.05) but not to the plasma steady-state levels ofmetoprolol, the degree of beta receptor blockade, and the decrease in PRA.