1. Immediate and long-term blood pressure-lowering activity of five β-adrenoreceptor antagonists with different ancillary pharmacological properties were compared in a randomized double-blind placebo controlled factorial trial in twenty-five previously untreated patients with stable uncomplicated essential hypertension.
2. In doses which produced similar reductions in exercise tachycardia, all drugs exerted similar antihypertensive activity, which was greater on systolic than diastolic pressure and greatest during exercise.
3. These effects were maximum within an hour and lasted for over 8 h after a single oral dose.
4. Blood pressure-lowering activity, particularly the reduction in exercise systolic pressure, was significantly related to the logarithm of the dose of each drug.
5. Anti-hypertensive activity was maximally enhanced after 4 weeks of sustained treatment at any given dose. There was no short-term habituation to treatment and substitution with placebo resulted in a return of the blood pressure to pretreatment values within 4 weeks without subsequent overshoot.
6. The blood pressure-lowering activity of these drugs was predominantly related to their common property of competitive antagonism of cardiac β-adrenoreceptors; their ancillary pharmacological properties, with the exception of intrinsic vasodilator activity, played little part in this response.