Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane.
Prazosin is a highly selective alpha 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 micrograms/kg i.v.) caused a differential dose-related depression of the evoked responses with ED50s of 81.5 micrograms/kg (peripheral stimulation) and 12.5 micrograms/kg (CNS stimulation) respectively; P less than 0.05. Pretreatment with rauwolscine (500 micrograms/kg i.v.) totally prevented the differential CNS sympatho-inhibition produced by prazosin. These results indicate that, although both CNS and peripheral sites of drug action are manifest, the ED50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct alpha 1-adrenoceptor blockade at the end organ. In addition, prazosin produces CNS sympatho-inhibition indirectly by means of an alpha 2-adrenoceptor mechanism.
Koss
M C
MC
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
D000758:Anesthesia; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects*; D010525:Peripheral Nerves / Q000378:metabolism*; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*
D011224:Prazosin