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.
Yang
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Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Chiba
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D013157:Splenic Artery / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000255:Adenosine Triphosphate; D007099:Imipramine; D009638:Norepinephrine; D014439:Tyramine