Sympathetic nervous activity and the pressor effect of noradrenaline under chronic alpha-beta-adrenoceptor blockade with labetalol in hypertension.

In 14 patients with essential hypertension, the influence of the alpha- and beta-adrenoceptor blocking drug labetalol on blood pressure, heart rate, plasma renin, plasma noradrenaline and pressor effect of exogenous noradrenaline was investigated during long-term treatment. During the initial four weeks of treatment, labetalol at a dose of 400 mg/day showed a slight effect only on supine blood pressure, whereas upright blood pressure was already lowered effectively after the second week of treatment (p less than 0.01). An increase in the mean dose to 850 mg/day had an additional blood pressure-lowering effect (p less than 0.001), whereby a preferential decrease of the orthostatic blood pressure was no longer apparent. Further increase in the mean dose to 1,000 mg/day at the end of the 12th week did not have an additional blood pressure-lowering effect. Body weight, plasma renin and plasma noradrenaline remained unchanged on labetalol treatment in the lowest and the highest dose. There was, however, an increased pressor effect of exogenous noradrenaline, i.e. an alpha-adrenoceptor antagonistic effect of labetalol was not detectable under these conditions. The cause of the increased pressor effect was a reduced elimination of noradrenaline from plasma, which is probably the consequence of an inhibition of the uptake 1 process by labetalol. During long-term treatment with the doses administered, the blood pressure-lowering effect of labetalol appears essentially to be the expression of the beta-adrenoceptor blocking properties of the drug.