Alpha-adrenoceptor blockade by labetalol during long-term dosing

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Abstract
The hypotensive effect of short-term labetalol, the .alpha.- and .beta.-adrenoceptore blocker, is greater in subjects in the orthostatic position, possibly because of the .alpha.-adrenoceptor blockade. During prolonged use the orthostatic blood pressure fall disappears. To verify whether or not this is due to reduction in .alpha.-blocking activity, the phenylephrine-induced increase in blood pressure was studied in 6 subjects with mild essential hypertension, before and after 3 and 6 days and 1 and 6 mo. of continuous treatment with 200 mg labetalol 3 times/day by mouth. At the same intervals, isoproterenol-induced tachycardia was followed to assess .beta.-blockade. After 3 days on labetalol, the log dose-response curve of phenylephrine-induced increase in blood pressure shifted to the right and the dose of agonist required to elicit a 20% increase in systolic pressure was 1.7 times that before treatment. There was a progressive decline in the dose of agonist that induced the same increase in pressure so that after 6 mo. of continuous labetalol it was the same as control. The amount of isoproterenol needed to induce a 20% increase in heart rate was 2-3 times that before labetalol and did not change throughout 6 mo. of therapy. These data indicate a decline in the .alpha.-adrenoceptor-blocking effect of oral labetalol without concomitant change in the degree of .beta.-adrenoceptor blockade. This might account for the disappearance of orthostatic hypotension early in the course of treatment and for some decrease in the antihypertensive efficacy of labetalol.