Pharmacological evidence that α2A- and α2C-adrenoceptors mediate the inhibition of cardioaccelerator sympathetic outflow in pithed rats

It has been suggested that the α2-adrenoceptors mediating cardiac sympatho-inhibition in pithed rats closely resemble the pharmacological profile of the α2A-adrenoceptor subtype. However, several lines of evidence suggest that more than one subtype may be involved. Thus, the present study has pharmacologically re-evaluated the receptor subtype(s) involved in the inhibitory effect of the α2-adrenoceptor agonist, B-HT 933, on the tachycardic responses elicited by selective cardiac sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) in desipramine-pretreated pithed rats. I.v. continuous infusions of B-HT 933 (30 μg/kg min), which failed to modify the tachycardic responses to exogenous noradrenaline, inhibited those induced by preganglionic (C7-T1) stimulation of the cardiac sympathetic outflow at all frequencies of stimulation (0.03–3 Hz). This cardiac sympatho-inhibitory response to B-HT 933 was: (1) unaltered by saline (1 ml/kg) or the antagonists BRL44408 (100 μg/kg; α2A) or imiloxan (3000 and 10,000 μg/kg; α2B); (2) partially antagonized by BRL44408 (300 μg/kg) or MK912 (10 μg/kg; α2C) given separately; and (3) completely antagonized by rauwolscine (300 μg/kg; α2), MK912 (30 μg/kg) or the combination of BRL44408 (300 μg/kg) plus MK912 (10 μg/kg). Moreover, the above doses of antagonists, which are high enough to block their respective receptors, failed to block per se the tachycardic responses to sympathetic stimulation. These results suggest that the cardiac sympatho-inhibition induced by B-HT 933 in pithed rats is mainly mediated by stimulation of α2A- and α2C-adrenoceptors.