THE EFFECTS OF PIPEROXAN ON UPTAKE OF NORADRENALINE AND OVERFLOW OF TRANSMITTER IN THE ISOLATED BLOOD PERFUSED SPLEEN OF THE CAT

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Abstract
The competitive α‐adrenoceptor blocking agent, piperoxan, in concentrations up to 2 × 10−4m, produced large dose‐dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz. At concentrations greater than 2 × 10 −4 m, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose‐dependent decrease in transmitter overflow. Phenoxybenzamine (10−4m) and desmethylimipramine (3 × 10−5m) produced further increases in transmitter overflow when added after piperoxan. Piperoxan (5.8 to 6.6 × 10−6m) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of [3H]‐(−)−noradrenaline, indicating that the drug does not inhibit uptake of the amine. Piperoxan produced dose‐dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 μg of (—)‐noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 × 10 −6m piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation. In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose‐response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens.