Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats

Abstract

This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α₂-adrenoceptors and to a lesser extent by I₁-imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α₂-adrenoceptors and I₁-imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α₂-adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats.

Keywords: (±)-noradrenaline bitartrate salt (PubChem CID: 5813); AGN 192403 hydrochloride (PubChem CID: 11957452); Agmatine; Agmatine sulfate salt (PubChem CID: 2794990); B-HT 933 dihydrochloride (PubChem CID: 169743); BU224 hydrochloride (PubChem CID: 11957470); Hypertension; I(1)-imidazoline receptor; Moxonidine; desipramine hydrochloride (PubChem CID: 65327); gallamine triethiodide (PubChem CID: 6172); moxonidine hydrochloride (PubChem CID: 11231255); rauwolscine hydrochloride (PubChem CID: 197067); α(2)-adrenoceptor.