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 stimulation s were performed at 1 and 10 Hz in the isolated, perfused canine splenic ar tery. Electrical nerve stimulation readily caused double-peaked vasoconstri ctions. The Ist-peak response at 1 Hz was not influenced by treatment with imipramine but the 2nd one was significantly enhanced by it. The 2nd-peak r esponse was markedly blocked by prazosin. An additional treatment with alph a,beta-methylene ATP, a P2X-purinoceptor desensitizer, abolished electrical stimulation-induced vascular responses that remained. At 10 Hz, the respon ses to electrical stimulation were not significantly influenced by imiprami ne. On the other hand, the imipramine treatment inhibited the tyramine-indu ced vasoconstriction but potentiated the noradrenaline-induced one. ATP-ind uced responses were not modified by imipramine. From these results, it is c oncluded that 1) the Ist-peaked constriction is mainly due to a P2X-purinoc eptor-dependent mechanism, 2) the 2nd one is mainly due to an al-adrenocept or-dependent mechanism, and 3) presynaptic uptake mechanisms may perform an important role in the regulation of vascular reactivity, especially at a l ow frequency.