Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes

Abstract

This study has investigated the role of the α₂-adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α_2A), imiloxan (3000μg/kg; α_2B), and JP-1302 (300μg/kg; α_2C) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I₁ antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α_2A- and α_2C-adrenoceptor subtypes and I₁-imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine.

Keywords: AGN 192403 hydrochloride (PubChem CID: 11957452); Agmatine; Agmatine sulfate salt (PubChem CID: 2794990); BRL 44408 maleate salt (PubChem CID: 71311805); I(1)-imidazoline receptor; JP-1302 dihydrochloride (PubChem CID: 540335); Sympatho-inhibition; desipramine hydrochloride (PubChem CID: 65327); gallamine triethiodide (PubChem CID: 6172); imiloxan hydrochloride (PudChem CID: 172975); α(2A)-adrenoceptor; α(2C)-adrenoceptor.