Evidence for a central depressor action of postsynaptic alpha 1-adrenergic receptor antagonists.
The effects of alpha-adrenergic receptor antagonists on sympathetic nervous discharge (SND) recorded from the external carotid and splanchnic nerves were studied in baroreceptor intact and denervated cats. Prazosin (50 microgram/kg, i.v.) produced a rapid fall in mean arterial pressure (MAP) and no significant change in heart rate (HR) in baroreceptor denervated cats. Prazosin administration was also associated with a prolonged inhibition of SND. Nerve activity was significantly reduced within 5 min of prazosin administration remained depressed throughout the 2 h observation period. Like prazosin, WB-4101 (0.5 mg/kg, i.v.) also produced significant reductions in MAP and SND. In addition, WB-4104 produced a transient bradycardia. The decreases in MAP and SND were reversed by piperoxane (0.5 mg/kg, i.v.). Both prazosin and WB-4101 inhibited the pressor response to i.v. norepinephrine. In baroreceptor intact cats, prazosin decreased MAP and SND, but did not affect HR. In contrast, phentolamine (1 mg/kg, i.v.) decreased MAP but increased SND and HR. These data indicate that the sympatholytic action of WB-4101 and prazosin results from a centrally mediated reduction in SND as well as a peripheral blockade of alpha-adrenergic receptors. These data further suggest that noradrenergic neurons normally facilitate the outflow of sympathetic nerve activity from the central nervous system.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D003000:Clonidine / Q000494:pharmacology; D003864:Depression, Chemical; D004146:Dioxanes / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D010883:Piperoxan / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011941:Receptors, Adrenergic; D010883:Piperoxan; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D011224:Prazosin; D010646:Phentolamine