Effect of Desipramine on the Effects of α‐Adrenoceptor Inhibitors on Pressor Responses and Release of Norepinephrine into Plasma of Pithed Rats

The role of neuronal uptake inhibition on the efficiency of α- and α2-antagonists in inhibiting pressor responses and the release of plasma catecholamines in pithed rats were studied. Prazosin. in doses which selectively blocked α-adrenoceptors (0.01–0.1 mg/kg). was more effective than yohimbine. a relatively selective α2-antagonist, in inhibiting stimulation-induced pressor responses. Yohimbine (0.1 - 1 mg/kg) potentiated or did not alter the pressor responses to stimulation, whereas it blocked pressor responses to administered norepineph-rine (NE) more effectively than did prazosin. Inhibition of uptake by desipramine (DMI). 0.3 mg/kg, did not affect prazosin inhibition of stimulation-induced pressor responses though it increased NE overflow into circulation. In yohimbine-treated rats. DMI potentiated significantly (p 0.001) both pressor and NE responses to stimulation. DMI partially reversed prazosin inhibition of pressor response to administered NE (p < 0.001) and potentiated the response in yohimbine-treated rats (p 0.01). The results are consistent with the view that endogenously released NE acts at intrajunctional α2-adrenoceptors. whereas exogenous NE acts predominantly at extrajunctional α2-adrenoceptors. The neuronal uptake site appears to be functionally (and perhaps anatomically) located outside the synaptic cleft, between intrajunctional α-postsynaptic receptors and extrajunctional α2-adrenoceptors.