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

Abstract

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.