Comparison of effects of urapidil and prazosin on vascular influence of circulating and neuronally released catecholamines in canine muscle vascular bed.
Two series of experiments were conducted in anesthetized dogs to compare the vascular effects of the alpha 1-adrenoceptor antagonists urapidil and prazosin. In the first series of experiments vasoconstrictor responses to sympathetic nerve stimulation and phenylephrine injected intraarterially were elicited in the pump-perfused hindlimb. Urapidil and prazosin administered intravenously in the doses of 2 and 0.25 mg/kg, respectively, were equivalent in their ability to block these responses. Yohimbine, an alpha 2-adrenoceptor antagonist, in the dose of 0.05 mg/kg, had no additional effect on the responses, but did decrease the vascular resistance after prazosin infusion. This suggested that urapidil, but not prazosin, exerted an alpha 2-blocking effect which decreased vascular resistance. In the second series of experiments the effect of urapidil administered intravenously was determined on the innervated and denervated gracilis muscle, after maximal alpha 1-adrenoceptor blockade with prazosin. The purpose of these experiments was to confirm whether or not urapidil had an additional effect on vascular resistance attributable to alpha 2-antagonism. Prazosin, 0.25 mg/kg followed by 0.50 mg/kg i.v., decreased vascular resistance in both the innervated and denervated gracilis muscles, and maximal alpha 1-blockade was achieved based on the blockade of the pressor responses to phenylephrine. A further reduction in vascular resistance was found after urapidil infusion, 2 mg/kg, which appears to be due to blockade of the effect of circulating catecholamines on alpha 2-adrenoceptors. The difference between the vascular resistance seen immediately following acute sympathetic denervation and the level achieved 15 min afterward appears to be due to the influence of circulating catecholamines.
D W
DW
Zeigler
B G
BG
Zimmerman
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D002395:Catecholamines; D010879:Piperazines; D010656:Phenylephrine; C015568:urapidil; D009638:Norepinephrine; D011224:Prazosin