Suppression of reflex tachycardia by central administration of the alpha-1 adrenoceptor antagonists urapidil and prazosin in anesthetized dogs

RJ Shebuski and BG Zimmerman

The present study was designed to determine if central administration of the alpha-1 adrenoceptor antagonists urapidil and prazosin would suppress baroreceptor-induced reflex tachycardia elicited by bradykinin and bilateral carotid occlusion in pentobarbital-anesthetized dogs. Urapidil and prazosin were infused intracisternally in doses ranging from 25 to 200 and 1 to 4 micrograms/kg, respectively. Urapidil suppressed reflex tachycardia elicited by bradykinin with little or no reduction in the pressor response to i.v. phenylephrine in vagotomized dogs or those with vagi intact. When reflex tachycardia was elicited by bilateral carotid occlusion urapidil suppressed the tachycardic response only when the vagi were intact. Prazosin also suppressed bradykinin-induced reflex tachycardia, but to a lesser degree than urapidil. Doses of prazosin that reduced reflex tachycardia also decreased the pressor response to i.v. phenylephrine. In order to authenticate that suppression of reflex tachycardia by urapidil was due to a central effect, urapidil was injected i.v. in doses shown previously to be effective intracisternally. When given i.v., urapidil failed to inhibit bradykinin-induced tachycardia, thus verifying a central site of action. No doses of urapidil or prazosin infused centrally affected basal blood pressure or heart rate. These data indicate that urapidil and prazosin, when administered intracisternally, suppress reflex tachycardia and that urapidil may be more effective than prazosin at this central site. Suppression of bradykinin-induced reflex tachycardia by urapidil and prazosin may be due to blockade of central alpha adrenoceptors, which are involved in the increased sympathetic outflow evoked by baroreceptor inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 234, Issue 2, pp. 456-462, 08/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics