Effects of Imipramine, an Uptake Inhibitor, on Double-Peaked Constrictor Responses to Periarterial Nerve Stimulation in Isolated, Perfused Canine Splenic Arteries

Using a cannula insertion method, periarterial nerve electrical stimulations were performed at 1 and 10 Hz in the isolated, perfused canine splenic artery. Electrical nerve stimulation readily caused double-peaked vasoconstrictions. The 1st-peak response at 1 Hz was not influenced by treatment with imipramine but the 2nd one was significantly enhanced by it. The 2nd-peak response was markedly blocked by prazosin. An additional treatment with alpha,beta-methylene ATP, a P2X-purinoceptor desensitizer, abolished electrical stimulation-induced vascular responses that remained. At 10 Hz, the responses to electrical stimulation were not significantly influenced by imipramine. On the other hand, the imipramine treatment inhibited the tyramine-induced vasoconstriction but potentiated the noradrenaline-induced one. ATP-induced responses were not modified by imipramine. From these results, it is concluded that 1) the 1st-peaked constriction is mainly due to a P2X-purinoceptor-dependent mechanism, 2) the 2nd one is mainly due to an alpha1-adrenoceptor-dependent mechanism, and 3) presynaptic uptake mechanisms may perform an important role in the regulation of vascular reactivity, especially at a low frequency.