Suppression of Reflex Tachycardia Following α-Adrenoceptor Blockade in Conscious Dogs

Abstract

The effects of the .alpha.-adrenoceptor antagonists urapidil and prazosin were compared as to their ability to suppress or enhance baroreceptor-induced reflex changes in heart rate in conscious dogs. Bradykinin was injected as an i.v. bolus to elicit a vasodepressor response and reflex tachycardia, and angiotensin II was used to produce opposite effects via baroreceptor activation. Urapidil, which is an .alpha.1- and .alpha.2-antagonist, was infused i.v. at 2 and 5 mg/kg and suppressed reflex tachycardia elicited by bradykinin at both dose. The reflex tachycardia suppression elicited by bradykinin was not evident with i.v. prazosin (0.25 and 0.625 mg/kg) and .alpha.1-antagonist. Reflex bradycardia elicited by angiotensin was unaffected by urapidil but enhanced by prazosin. Therefore, urapidil may have a selective effect in suppressing cardiac sympathetic reflexes with no apparent effect on vagal reflexes. Urapidil and prazosin produced similar decreases in arterial blood pressure with no long-term effects on heart rate, and .alpha.-receptor postjunctional blockade by both agents was equivalent, as determined by i.v. phenylephrine injection. The urapidil suppression of reflex tachycardia could be eliminated by guanethidine pretreatment, indicating that a cardiosympathoinhibitory effect by ruapidil was involved.