, Volume 329, Issue 2, pp 162-166

Cardiac postjunctional supersensitivity to β-agonists after chronic chemical sympathectomy with 6-hydroxydopamine

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The sensitivity to sympathomimetic amines of isolated atria removed from sham-injected and 6-hydroxydopamine-treated (6-OHDA) guinea-pigs was examined in the presence of an extraneuronal uptake blocker and an α-adrenoceptor antagonist. Three weeks of pretreatment with 6-OHDA resulted in leftwards shifts of the dose-response curves for the positive chronotropic and inotropic responses of right and left atria to isoprenaline. The responses to the partial agonist salbutamol were also potentiated after 6-OHDA pretreatment, revealed as an increase in the maximum response relative to isoprenaline.

The supersensitivity was post-synaptic in origin and independent of changes in disposition or metabolism, since it was observed with agonists immune to neuronal uptake and O-methylation, and in the presence of extraneuronal uptake inhibition by metanephrine. It was also specific for the β-adrenoceptor, no supersensitivity to histamine being found. In the right atria, the supersensitivity was partially masked by an opposing depressant effect after 6-OHDA pretreatment which was observed with histamine.

Dissociation constants (K A) for the left atrial inotropic responses to orciprenaline were determined by use of the antagonist Ro 03-7894. Atria from 6-OHDA-pretreated animals were supersensitive to orciprenaline, but the K A value did not differ from that after sham injection. It could therefore be concluded that the increase in sensitivity was not due to an increase in affinity for the β-adrenoceptor.