Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane

Abstract Prazosin is a highly selective α 1 -adrenoceptor antagonist that decreases blood pressure by actions on both the peripheral and central (CNS) divisions of the nervous system. The present investigation was undertaken in an attempt to characterize the relative contribution of these two sympatholytic sites of action. Submaximal contractions of the nictitating membranes were evoked by electrical stimulation of the preganglionic cervical sympathetic nerve trunk and by stimulation of the posterior hypothalamus in anesthetized cats. In initial control experiments, phenoxybenzamine (0.1–3.0 mg/kg i.v.) produced an equivalent depression of evoked nictitating membrane responses from both peripheral and CNS sites of activation which suggests only a peripheral blocking action as well as functional equivalence of the intensity of CNS and peripheral nerve stimulation. In contrast, prazosin (3–300 μg/kg i.v.) caused a differential dose-related depression of the evoked responses with ED 50 s of 81.5 μg/kg (peripheral stimulation) and 12.5 μg/kg (CNS stimulation) respectively; P 50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct α 1 -adrenoceptor blockade at the end organ. In additiom, prazosin produces CNS sympatho-inhibition indirectly by means of an α 2 -adrenoceptor mechanism.