1. Twelve hypertensive patients with cardiomegaly were treated with equivalent antihypertensive doses of prazosin (11 weeks) and β-adrenoceptor-blocking drug (9 weeks) in random crossover fashion.
2. At the end of each treatment period haemodynamic assessment included the response to isometric handgrip exercise (4 min at 30% of maximum voluntary contraction).
3. Resting cardiac index and heart rate were higher on prasozin although the latter was only 65 beats/min. Systemic vascular resistance and left ventricular filling pressure were insignificantly higher on β-adrenoceptor-blocking drug.
4. During isometric handgrip the blood pressure rise was similar on the two regimens, but the mechanism whereby it was achieved was quite different. On prazosin an increase in cardiac output accounted for the pressor response with virtually no change in systemic vascular resistance, whereas on β blockade there was a flat cardiac output response with a marked increase in the systemic vascular resistance.
5. Ventricular function curves indicated a predominant utilization of the Frank-Starling mechanism during β blockade, whereas enhanced contractility played a major role during prazosin treatment.
6. The isometric exercise response pattern during prazosin treatment resembles that in normal subjects whereas in the β blockade phase it corresponded to that in untreated hypertensive patients with left ventricular hypertrophy or cardiomegaly or to that in congestive heart failure patients.
7. There was no evidence of harmful effects of combined pre- and after-load reduction in hypertensive patients with cardiomegaly and normal filling pressure, even under conditions of moderately severe cardiac loading with isometric exercise.