Combined central and peripheral sympathetic blockade: absence of additive antihypertensive effects

Two antihypertensive agents that inhibits sympathetic activity by differing pharmacologic mechanisms, the centrally-acting alpha-adrenergic agonist, clonidine, and the peripheral alpha-adrenergic antagonist, prazosin, were compared and also given in combination in 24 patients with essential hypertension. The patients were randomized into two groups; 11 received chlorthalidone (50 mg) daily throughout the protocol, whereas 13 received no diuretic. In the 13 patients not receiving the diuretic, supine mean blood pressure fell by 11.0 +/- 3.5 mmHg (p less than 0.01) with clonidine (0.3 mg daily), 5.5 +/- 2.9 mm Hg (p less than 0.05) with prazosin (15 mg daily), and 12.7 +/- 5.2 mmHg (p less than 0.02) with the combination. In the 11 patients concurrently receiving chlorthalidone, supine mean blood pressure fell by 9.5 +/- 2.0 mmHg (p less than 0.01) when clonidine was added, 2.3 +/- 1.9 mmHg (ns) when prazosin was added, and 7.9 +/- 2.1 mmHg (p less than 0.01) with the combination. In both the presence and absence of concurrent diuretic treatment, the blood pressure-lowering effects of clonidine were greater than those of prazosin, but were not different from the antihypertensive effects of the combination of clonidine and prazosin. Therefore, the simultaneous administration of clonidine and prazosin in the doses used in this study does not appear to be more effective than clonidine alone in the treatment of patients with hypertension.