Magnitude and mechanisms of the antihypertensive action of labetalol, including ambulatory assessment

Attempts have been made to improve on the actions of 8-adrenoceptor blocking agents by eliminating effects on bronchial muscle and peripheral vessels. Labetalol possesses both α- and β-adrenoceptor blocking properties and has the potential to reverse some unwanted peripheral side-effects of β- adrenoceptor blockers (Gilmore et al., 1970) by directly lowering vascular resistance (Maxwell, 1973) and possibly by antagonising α-adrenoceptor mediated bronchoconstriction (Skinner et al., 1975). Labetalol can be expected to cause less bradycardia than other β-adrenoceptor blockers, except those with intrinsic sympathomimetic activity (Man in't Veld & Schalekamp, 1982). Because of its dual action in blocking a- and 8-adrenoceptors, the drug is potentially useful in a wider spectrum of hypertensives than agents having effects only on the β-adrenoceptor. The ratio of α- to β-adrenoceptor effect of labetalol is biased towards the latter (Richards et al., 1977), and is known to change further in that direction with increasing dosage. While α-adrenoceptor blockade carries with it the potential for orthostatic blood pressure effects (Williams et al., 1979), there is evidence that with labetalol this is only a problem in the presence of diuretic induced plasma volume depletion (Hunyor et al., 1980). The 24 h antihypertensive efficacy of thrice daily labetalol has been assessed in moderate to severe hypertension in a non-randomised study (Balasubramanian et al., 1979a). In contrast, the present study examines the effect of a lower dose in the more common situation of mild hypertension. A twice daily regimen which most patients find practical, was used in a randomised, placebo controlled fashion. Beside studying the 24 h blood pressure pattern, particular note was taken of the blood pressure at a time most remote from dosing, at which time the effect of contrived physiological stress (static and dynamic exercise) was also examined. The response to dynamic exercise was used as an index of β-adrenoceptor blockade (McDevitt & Shand, 1976; Jennings et al., 1981). The reflex control of blood pressure during Valsalva's manoeuvre was assessed to ascertain whether the effect of labetalol is related to a significant a-adrenoceptor blocking action (Korner et al., 1979).