Suppression of reflex tachycardia following alpha-adrenoceptor blockade in conscious dogs: comparison of urapidil with prazosin.
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 intravenous bolus to elicit a vasodepressor response and reflex tachycardia, and angiotensin II was utilized to produce opposite effects via baroreceptor activation. Urapidil, which is an alpha 1- and alpha 2-antagonist, was infused intravenously at 2 and 5 mg/kg, and suppressed reflex tachycardia elicited by bradykinin at both dose levels. The suppression of reflex tachycardia elicited by bradykinin was not evident with intravenous prazosin (0.25 and 0.625 mg/kg), an alpha 1-antagonist. Reflex bradycardia elicited by angiotensin was not affected by urapidil but was enhanced by prazosin. Therefore, urapidil may have a selective effect in suppressing cardiac sympathetic reflexes with no apparent effect on vagal reflexes. Both urapidil and prazosin produced similar decreases in arterial blood pressure with no long-term effects on heart rate, and the degree of alpha-receptor postjunctional blockade by both agents was judged to be equivalent, as determined by intravenous phenylephrine injection. The suppression of reflex tachycardia by urapidil could be eliminated by guanethidine pretreatment, indicating that a cardiosympathoinhibitory effect by urapidil was involved.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D011799:Quinazolines; D000804:Angiotensin II; C015568:urapidil; D003000:Clonidine; D001920:Bradykinin; D011224:Prazosin; D006145:Guanethidine