Comparative Effects of Prazosin and Phenoxybenzamine on Arterial Blood Pressure, Heart Rate, and Plasma Catecholamines in Essential Hypertension

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We investigated the possibility that selective blockade of postjunctional α-adrenergic receptors results in an enhanced antihypertensive response relative to that observed with α-adrenergic antagonists, which are less selective and thus block both pre- and postjunctional α-receptors. The antihypertensive efficacy of prazosin (a selective postjunctional antagonist) was compared with that of phenoxybenzamine (a less selective postjunctional antagonist) in a double-blind, placebo-control, randomized, crossover study in 11 patients with essential hypertension. Both drugs produced similar significant reductions in standing mean arterial pressure (MAP) from 124 ± 3 to 104 ± 5 mm Hg (p < 0.001) and 122 ± 3 to 109 ± 7 mm Hg (p < 0.025), respectively, after four weeks of therapy. However, the increments in plasma norepinephrine (PNE) concentration associated with these falls in MAP from 622 ± 90 to 1,025 ± 100 pg/ml (p < 0.01) and from 554 ± 80 to 1,029 ± 168 pg/ml (p < 0.01), respectively, were not significantly different for the two drugs. Heart rate also increased significantly, although the increase after prazosin was not sustained. In contrast to the responses in the standing position, only prazosin produced a significant fall in supine MAP from 118 ± 3 to 107 ± 3 mm Hg (p < 0.001) and an increase in PNE concentration from 283 ± 39 to 415 ± 50 pg/ml (p < 0.05). Heart rate increased marginally after prazosin and remained unchanged with phenoxybenzamine therapy. Thus prazosin is a more effective antihypertensive agent than phenoxybenzamine. However, the present study suggests that the enhanced antihypertensive efficacy of prazosin is not due to its selectivity for the postjunctional α-adrenergic receptor.

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