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

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 (3 μg/kg min); (2) partially inhibited by B-HT 933 (30 μg/kg min), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100 μg/kg min), moxonidine (10 μg/kg min) or agmatine (1000 and 3000 μg/kg min) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000 μg/kg min agmatine. In SHR, 300 μg/kg rauwolscine failed to block the sympatho-inhibition to 100 μg/kg min B-HT 933 or 10 μg/kg min moxonidine, but 1000 μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000 μg/kg AGN 192403 or 300 μg/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.