Comparative anti-hypertensive effectiveness of beta-adrenoreceptor antagonists with different pharmacological...

1. Immediate and long-term blood pressure-lowering activity of five beta-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 anti-hypertensive 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 beta-adrenoreceptors; their ancillary pharmacological properties, with the exception of intrinsic vasodilator activity, played little part in this response.